Photolabile ruthenium complexes to cage and release a highly cytotoxic anticancer agent.

PubMed

Wei, Jianhua; Renfrew, Anna K

2018-02-01

CHS-828 (N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N″-4-pyridyl guanidine) is an anticancer agent with low bioavailability and high systemic toxicity. Here we present an approach to improve the therapeutic profile of the drug using photolabile ruthenium complexes to generate light-activated prodrugs of CHS-828. Both prodrug complexes are stable in the dark but release CHS-828 when irradiated with visible light. The complexes are water-soluble and accumulate in tumour cells in very high concentrations, predominantly in the mitochondria. Both prodrug complexes are significantly less cyototoxic than free CHS-828 in the dark but their toxicity increases up to 10-fold in combination with visible light. The cellular responses to light treatment are consistent with release of the cytotoxic CHS-828 ligand. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical synthesis of water-soluble, chiral conducting-polymer complexes

DOEpatents

Wang, Hsing-Lin; McCarthy, Patrick A.; Yang, Sze Cheng

2003-01-01

The template-guided synthesis of water-soluble, chiral conducting polymer complexes is described. Synthesis of water-soluble polyaniline complexes is achieved by carefully controlling the experimental parameters such as; acid concentration, ionic strength, monomer/template ratio, total reagent concentration, and order of reagent addition. Chiral (helical) polyaniline complexes can be synthesized by addition of a chiral inducing agent (chiral acid) prior to polymerization, and the polyaniline helix can be controlled by the addition of the (+) or (-) form of the chiral acid. Moreover the quantity of chiral acid and the salt content has a significant impact on the degree of chirality in the final polymer complexes. The polyaniline and the template have been found to be mixed at the molecular level which results in chiral complexes that are robust through repeated doping and dedoping cycles.

Solubility enhancement of a bisnaphthalimide tumoricidal agent, DMP 840, through complexation.

PubMed

Raghavan, K S; Nemeth, G A; Gray, D B; Hussain, M A

1996-10-01

The purpose of this research was to enhance the aqueous solubility of DMP 840 by complexation with water-soluble and nontoxic agents, and to understand the nature of the interactions involved in complex formation using nuclear magnetic resonance (1H-NMR). The solubility of DMP 840 in water, saline, acetate buffers, and cosolvent mixtures was determined by high-performance liquid chromatography, and the effect of nicotinamide and pyridoxine concentrations on the solubility of DMP 840 was examined by the phase solubility method. 1H-NMR spectra were acquired in deuterated acetate buffer at 400 MHz on a Varian Unity-400 spectrometer. The aqueous solubility of DMP 840 was sensitive to the presence of chloride and acetate anions in solution, and did not improve in the presence of cosolvents. The use of the nontoxic and water-soluble complex-forming agents nicotinamide and pyridoxine, however, resulted in a linear increase in the aqueous solubility of DMP 840 with both ligands. The solubilization appears to be due to formation of 1:1 complexes between DMP 840 and the bioorganic ligands. The complexation constants were 15.57 M-1 for the DMP 840:nicotinamide complex and 13.36 M-1 for the DMP 840:pyridoxine complex. The NMR results indicate that the interaction is a result of vertical or plane-to-plane stacking and the complexation constants were in agreement with that obtained by phase solubility. The results suggest that the aqueous solubility of a poorly water soluble drug substance such as DMP 840 can be significantly enhanced by its complexation with water-soluble and nontoxic agents.

Anticancer, antibacterial and antifungal activity of new ni (ii) and cu (ii) complexes of imidazole-phenanthroline derivatives.

PubMed

Moghadam, Mahboube Eslami; Divsalar, Adeleh; Zare, Marziye Shahraki; Gholizadeh, Roghayeh; Mahalleh, Doran; Saghatforosh, Lotfali; Sanati, Soheila

2017-11-02

Two new nickel(II) and copper(II) complexes of 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1,10]Phenanthroline (FIP) and 2-(thiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (TIP), imidazophen derivatives were synthesized. The structures of the compounds were determined by UV-visible and FT-IR spectroscopic methods and elemental analysis. The biological activities of Ni and Cu complexes, as anticancer agents, were tested against chronic myelogenous leukemia cell line, K562, at micromolar concentration. The MTT studies showed Cc 50 values are 21 and 160 µM for Cu and Ni(II) complexes, respectively; suggesting that Ni (II) complex has Cc 50 almost seven times of that obtained for cisplatin. Biological activity of the Ni(II) and Cu(II) complexes were also assayed against selective microorganisms by disc diffusion method. These results showed that the Cu(II) complex is antifungal agent but Ni(II) complex has antibacterial activity.

Gallium(iii) and iron(iii) complexes of quinolone antimicrobials.

PubMed

Mjos, Katja Dralle; Cawthray, Jacqueline F; Polishchuk, Elena; Abrams, Michael J; Orvig, Chris

2016-08-16

Iron is an essential nutrient for many microbes. According to the "Trojan Horse Hypothesis", biological systems have difficulties distinguishing between Fe(3+) and Ga(3+), which constitutes the antimicrobial efficacy of the gallium(iii) ion. Nine novel tris(quinolono)gallium(iii) complexes and their corresponding iron(iii) analogs have been synthesized and fully characterized. Quinolone antimicrobial agents from three drug generations were used in this study: ciprofloxacin, enoxacin, fleroxacin, levofloxacin, lomefloxacin, nalidixic acid, norfloxacin, oxolinic acid, and pipemidic acid. The antimicrobial efficacy of the tris(quinolono)gallium(iii) complexes was studied against E. faecalis and S. aureus (both Gram-positive), as well as E. coli, K. pneumonia, and P. aeruginosa (all Gram-negative) in direct comparison to the tris(quinolono)iron(iii) complexes and the corresponding free quinolone ligands at various concentrations. For the tris(quinolono)gallium(iii) complexes, no combinational antimicrobial effects between Ga(3+) and the quinolone antimicrobial agents were observed.

Effect of Molecular Structure on Modulation of Passivation Films on Copper Chemical Mechanical Planarization

NASA Astrophysics Data System (ADS)

Mlynarski, Amy

In order to optimize the chemical mechanical planarization (CMP) process, there is a need to further understand the synergistic relationship between chemical and mechanical parameters to enhance the polishing process. CMP chemistry is very complex, as it contains complexing agents, oxidizing agents, passivating agents, and abrasive particles. This variety of components ensues chaos within the system, which complicates the understanding of the direct impact each component has on the CMP process. In order for there to be efficiency in the polishing process, specifically for copper (Cu) polishing, the chemistry must create a softened passivation layer on the Cu surface that is able to be readily removed by applied mechanical abrasion. Focusing on Cu CMP, the oxidation of Cu to Cu2+ needs to be thoroughly understood in order to probe the formation of creating this ideal passivated layer, which protects recessed Cu regions. The type of film that is formed, the strength of the film, and even the efficiency of film removal will be altered depending on the chemistry of interaction at the Cu surface. This thesis focuses on understanding the working mechanism of the film formation on Cu, depending on the passivating agent added to the system. The different passivating agents used, more specifically benzotriazole (BTA), triazole (TAZ), salicylhydroxamic acid (SHA), and benzimidazole (BIA), have all been known to create a light coat of protection on the recessed metal, providing corrosion resistance. In order to study the differences in these films, many different techniques can be utilized to characterize the films, such as electrochemical scans, referred to as Tafel plots, which will be performed to compare the differences of the films. By altering the temperature within the system, the activation energy for each system can also be determined as another way to characterize the density of the passive film formed. Furthermore, the generation of *OH will be monitored since the formation of *OH is imperative for catalyzing the Cu-amino acid complexes, necessary for obtaining adequate removal rates. The amount of *OH generated from each system would have a direct correlation to the polishing performance for the different systems. Additionally, the effect of changing mechanical parameters or consumables used will alter the polish, more specifically the amount of friction generated during the polishes. This work discovered that when comparing all of the different types of inhibitors, there was a significant difference seen in the type of film formed as well as the stability of the film, strongly dependent on the concentration of the corrosion inhibitor. The calculated activation energy showed a direct correlation to the concentration of the corrosion inhibitor; more specifically, as the concentration of the inhibitor increases, so does the activation energy. By looking at the generated amount of *OH for the complexes, more specifically BTA and SHA, there is a minimal amount of *OH generated within the system compared to that of TAZ and BIA which resemble more like a system containing no inhibitor at all. This would once again show how the structure determines function of the inhibitor in regards to how the complex changes for the different molecules. The removal rates for these systems, both at 100 ppm and 500 ppm, show a strong correlation to the previously discussed activation energies. BTA shows extremely low removal rates, which seems to be diminished at even higher concentration, since the film created is so dense due to the pi-pi electron interactions. Similar trends are seen in the results from TAZ where the removal rates decrease as the concentration of the inhibitor increases. Furthermore, SHA shows significant material removal rates (MRR) at lower concentrations, but the rates are vastly different when increasing the concentration to 500 ppm. This could be because the complex that forms with the surface is a stable ring-like complex, but once enough inhibitor is added, the SHA complex covers the surface entirely, eliminating any chance of Cu-glycine interaction, which would promote removal rate. Unlike the other inhibitors, the removal rates for BIA show that as the concentration of the inhibitor increases, the removal rates significantly increase as well. Since this inhibitor forms a "weaker" complex, comparatively, the more inhibitor added would allow for more of the Cu-glycine interactions to take place.

Complexation of buffer constituents with neutral complexation agents: part I. Impact on common buffer properties.

PubMed

Riesová, Martina; Svobodová, Jana; Tošner, Zdeněk; Beneš, Martin; Tesařová, Eva; Gaš, Bohuslav

2013-09-17

The complexation of buffer constituents with the complexation agent present in the solution can very significantly influence the buffer properties, such as pH, ionic strength, or conductivity. These parameters are often crucial for selection of the separation conditions in capillary electrophoresis or high-pressure liquid chromatography (HPLC) and can significantly affect results of separation, particularly for capillary electrophoresis as shown in Part II of this paper series (Beneš, M.; Riesová, M.; Svobodová, J.; Tesařová, E.; Dubský, P.; Gaš, B. Anal. Chem. 2013, DOI: 10.1021/ac401381d). In this paper, the impact of complexation of buffer constituents with a neutral complexation agent is demonstrated theoretically as well as experimentally for the model buffer system composed of benzoic acid/LiOH or common buffers (e.g., CHES/LiOH, TAPS/LiOH, Tricine/LiOH, MOPS/LiOH, MES/LiOH, and acetic acid/LiOH). Cyclodextrins as common chiral selectors were used as model complexation agents. We were not only able to demonstrate substantial changes of pH but also to predict the general complexation characteristics of selected compounds. Because of the zwitterion character of the common buffer constituents, their charged forms complex stronger with cyclodextrins than the neutral ones do. This was fully proven by NMR measurements. Additionally complexation constants of both forms of selected compounds were determined by NMR and affinity capillary electrophoresis with a very good agreement of obtained values. These data were advantageously used for the theoretical descriptions of variations in pH, depending on the composition and concentration of the buffer. Theoretical predictions were shown to be a useful tool for deriving some general rules and laws for complexing systems.

Effect of pH and sulfur precursor concentration on electrochemically deposited CZTS thin films using glycine as the complexing agent

NASA Astrophysics Data System (ADS)

Paraye, Akanksha; Sani, Rabiya; Ramachandran, Manivannan; Selvam, Noyel Victoria

2018-03-01

Copper zinc tin sulfide (CZTS) a promising quaternary chalcogenide material was deposited using single step electrodeposition using glycine as the complexing agent. The deposition was studied at different sulfur concentrations and at different pH. The pH of the electrolyte was found to influence the stoichiometry of the deposits significantly. The deposits formed at pH 2.5 showed satisfactory stoichiometry. The thickness of the deposits was observed to decrease with increase in sulfur concentration and pH. The transmission electron spectroscopy analysis showed the formation of flower shaped core shell particles from the electrolyte that contained 80 mM sulfur precursor at pH 2.5. The band gap of the deposits was found to be in the range from 1.57 eV to 2.1 eV. X-ray diffraction analysis showed that the as synthesized particles were amorphous in nature, the crystallinity of which improved with annealing. The Mott Schottky analysis of the deposits in 0.1 M sodium perchlorate showed that the particles exhibited p-type conductivity.

Paramagnetic liposomes as innovative contrast agents for magnetic resonance (MR) molecular imaging applications.

PubMed

Terreno, Enzo; Delli Castelli, Daniela; Cabella, Claudia; Dastrù, Walter; Sanino, Alberto; Stancanello, Joseph; Tei, Lorenzo; Aime, Silvio

2008-10-01

This article illustrates some innovative applications of liposomes loaded with paramagnetic lanthanide-based complexes in MR molecular imaging field. When a relatively high amount of a Gd(III) chelate is encapsulated in the vesicle, the nanosystem can simultaneously affect both the longitudinal (R(1)) and the transverse (R(2)) relaxation rate of the bulk H2O H-atoms, and this finding can be exploited to design improved thermosensitive liposomes whose MRI response is not longer dependent on the concentration of the probe. The observation that the liposome compartmentalization of a paramagnetic Ln(III) complex induce a significant R(2) enhancement, primarily caused by magnetic susceptibility effects, prompted us to test the potential of such agents in cell-targeting MR experiments. The results obtained indicated that these nanoprobes may have a great potential for the MR visualization of cellular targets (like the glutamine membrane transporters) overexpressing in tumor cells. Liposomes loaded with paramagnetic complexes acting as NMR shift reagents have been recently proposed as highly sensitive CEST MRI agents. The main peculiarity of CEST probes is to allow the MR visualization of different agents present in the same region of interest, and this article provides an illustrative example of the in vivo potential of liposome-based CEST agents.

Rinsing paired-agent model (RPAM) to quantify cell-surface receptor concentrations in topical staining applications of thick tissues

NASA Astrophysics Data System (ADS)

Xu, Xiaochun; Wang, Yu; Xiang, Jialing; Liu, Jonathan T. C.; Tichauer, Kenneth M.

2017-06-01

Conventional molecular assessment of tissue through histology, if adapted to fresh thicker samples, has the potential to enhance cancer detection in surgical margins and monitoring of 3D cell culture molecular environments. However, in thicker samples, substantial background staining is common despite repeated rinsing, which can significantly reduce image contrast. Recently, ‘paired-agent’ methods—which employ co-administration of a control (untargeted) imaging agent—have been applied to thick-sample staining applications to account for background staining. To date, these methods have included (1) a simple ratiometric method that is relatively insensitive to noise in the data but has accuracy that is dependent on the staining protocol and the characteristics of the sample; and (2) a complex paired-agent kinetic modeling method that is more accurate but is more noise-sensitive and requires a precise serial rinsing protocol. Here, a new simplified mathematical model—the rinsing paired-agent model (RPAM)—is derived and tested that offers a good balance between the previous models, is adaptable to arbitrary rinsing-imaging protocols, and does not require calibration of the imaging system. RPAM is evaluated against previous models and is validated by comparison to estimated concentrations of targeted biomarkers on the surface of 3D cell culture and tumor xenograft models. This work supports the use of RPAM as a preferable model to quantitatively analyze targeted biomarker concentrations in topically stained thick tissues, as it was found to match the accuracy of the complex paired-agent kinetic model while retaining the low noise-sensitivity characteristics of the ratiometric method.

1H NMR analysis of complexation of hydrotropic agents nicotinamide and caffeine with aromatic biologically active molecules in aqueous solution

NASA Astrophysics Data System (ADS)

Lantushenko, Anastasia O.; Mukhina, Yulia V.; Veselkov, Kyrill A.; Davies, David B.; Veselkov, Alexei N.

2004-07-01

NMR spectroscopy has been used to elucidate the molecular mechanism of solubilization action of hydrotropic agents nicotinamide (NA) and caffeine (CAF). Hetero-association of NA with riboflavine-mononucleotide (FMN) and CAF with low soluble in aqueous solution synthetic analogue of antibiotic actinomycin D, actinocyl-bis-(3-dimethylaminopropyl) amine (Actill), has been investigated by 500 MHz 1H NMR spectroscopy. Concentration and temperature dependences of proton chemical shifts have been analysed in terms of a statistical-thermodynamic model of indefinite self- and heteroassociation of aromatic molecules. The obtained results enable to conclude that NA-FMN and CAF-Actill intermolecular complexes are mainly stabilized by the stacking interactions of the aromatic chromophores. Hetero-association of the investigated molecules plays an important role in solubilization of aromatic drugs by hydrotropic agents nicotinamide and caffeine.

A highly stable l-alanine-based mono(aquated) Mn(ii) complex as a T1-weighted MRI contrast agent.

PubMed

Khannam, Mahmuda; Weyhermüller, Thomas; Goswami, Upashi; Mukherjee, Chandan

2017-08-08

The synthesized lithium (S)-6,6'-(1-carboxyethylazanediyl)bis(methylene)dipicolinate (Li 3 cbda) is a new chiral, alanine-based ligand bearing two picolinate functionalities. The trianionic form of the ligand [(cbda) 3- ] constitutes a seven-coordinate, water-soluble, pentagonal bipyramidal Mn(ii) complex (1). The structural analysis reveals the presence of a water coordinating site in the complex. The complex is thermodynamically very stable, and the stability is not affected by the presence of physiological anions (HCO 3 - , PO 4 3- , and F - ). The pH of the medium exerts a small effect on the stability of the complex. The r 1 relaxivity of 3.02 mM -1 s -1 is exhibited by the complex at 1.41 T, pH ∼7.4, and 25 °C. Phantom images obtained via a clinical MRI BRIVO MR355 system established concentration-dependent signal enhancement by the complex. The cytotoxicity test confirmed complex 1 as a biocompatible potential T 1 -weighted MRI contrast agent.

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

Boggs, S. Jr.; Livermore, D.; Seitz, M.G.

Dissolved humic substances (humic and fulvic acids) occur in surface waters and groundwaters in concentrations ranging from less than 1 mg(C)/L to more than 100 mg(C)/L. Humic substances are strong complexing agents for many trace metals in the environment and are also capable of forming stable soluble complexes or chelates with radionuclides. Concentrations of humic materials as low as 1 mg(C)/L can produce a detectable increase in the mobility of some actinide elements by forming soluble complexes that inhibit sorption of the radionuclides onto rock materials. The stability of trace metal- or radionuclide-organic complexes is commonly measured by an empiricallymore » determined conditional stability constant (K'), which is based on the ratio of complexed metal (radionuclide) in solution to the product concentration of uncomplexed metal and humic complexant. Larger values of stability constants indicate greater complex stability. The stability of radionuclide-organic complexes is affected both by concentration variables and envionmental factors. In general, complexing is favored by increased of radionuclide, increased pH, and decreased ionic strength. Actinide elements are generally most soluble in their higher oxidation states. Radionuclides can also form stable, insoluble complexes with humic materials that tend to reduce radionuclide mobility. These insoluble complexes may be radionuclide-humate colloids that subsequently precipitate from solution, or complexes of radionuclides and humic substances that sorb to clay minerals or other soil particulates strongly enough to immobilize the radionuclides. Colloid formation appears to be favored by increased radionuclide concentration and lowered pH; however, the conditions that favor formation of insoluble complexes that sorb to particulates are still poorly understood. 129 refs., 25 figs., 19 tabs.« less

Influence of anesthesia on cerebral blood flow, cerebral metabolic rate, and brain functional connectivity.

PubMed

Bonhomme, Vincent; Boveroux, Pierre; Hans, Pol; Brichant, Jean François; Vanhaudenhuyse, Audrey; Boly, Melanie; Laureys, Steven

2011-10-01

To describe recent studies exploring brain function under the influence of hypnotic anesthetic agents, and their implications on the understanding of consciousness physiology and anesthesia-induced alteration of consciousness. Cerebral cortex is the primary target of the hypnotic effect of anesthetic agents, and higher-order association areas are more sensitive to this effect than lower-order processing regions. Increasing concentration of anesthetic agents progressively attenuates connectivity in the consciousness networks, while connectivity in lower-order sensory and motor networks is preserved. Alteration of thalamic sub-cortical regulation could compromise the cortical integration of information despite preserved thalamic activation by external stimuli. At concentrations producing unresponsiveness, the activity of consciousness networks becomes anticorrelated with thalamic activity, while connectivity in lower-order sensory networks persists, although with cross-modal interaction alterations. Accumulating evidence suggests that hypnotic anesthetic agents disrupt large-scale cerebral connectivity. This would result in an inability of the brain to generate and integrate information, while external sensory information is still processed at a lower order of complexity.

Book Review:

NASA Astrophysics Data System (ADS)

McKane, Alan

2003-12-01

This is a book about the modelling of complex systems and, unlike many books on this subject, concentrates on the discussion of specific systems and gives practical methods for modelling and simulating them. This is not to say that the author does not devote space to the general philosophy and definition of complex systems and agent-based modelling, but the emphasis is definitely on the development of concrete methods for analysing them. This is, in my view, to be welcomed and I thoroughly recommend the book, especially to those with a theoretical physics background who will be very much at home with the language and techniques which are used. The author has developed a formalism for understanding complex systems which is based on the Langevin approach to the study of Brownian motion. This is a mesoscopic description; details of the interactions between the Brownian particle and the molecules of the surrounding fluid are replaced by a randomly fluctuating force. Thus all microscopic detail is replaced by a coarse-grained description which encapsulates the essence of the interactions at the finer level of description. In a similar way, the influences on Brownian agents in a multi-agent system are replaced by stochastic influences which sum up the effects of these interactions on a finer scale. Unlike Brownian particles, Brownian agents are not structureless particles, but instead have some internal states so that, for instance, they may react to changes in the environment or to the presence of other agents. Most of the book is concerned with developing the idea of Brownian agents using the techniques of statistical physics. This development parallels that for Brownian particles in physics, but the author then goes on to apply the technique to problems in biology, economics and the social sciences. This is a clear and well-written book which is a useful addition to the literature on complex systems. It will be interesting to see if the use of Brownian agents becomes a standard tool in the study of complex systems in the future.

Synthesis of ZnS films on Si(100) wafers by using chemical bath deposition assisted by the complexing agent ethylenediamine

NASA Astrophysics Data System (ADS)

Zhu, He-Jie; Wang, Xue-Mei; Gao, Xiao-Yong

2015-07-01

Low-cost synthesis of high-quality ZnS films on silicon wafers is of much importance to the ZnSbased heterojunction blue light-emitting device integrated with silicon. Thus, a series of ZnS films were chemically synthesized at low cost on Si(100) wafers at 353 K under a mixed acidic solution with a pH of 4 with zinc acetate and thioacetamide as precursors and with ethylenediamine and hydrochloric acid as the complexing agent and the pH value modifier, respectively. The effects of the ethylenediamine concentration on the crystallization, surface morphology, and optical properties of the ZnS films were investigated by using X-ray diffractometry, scanning electron microscopy, spectrophotometry, and fluorescence spectroscopy. A mechanism for the formation of ZnS film under an acidic condition was also proposed. All of the ZnS films were polycrystalline in nature, with a dominant cubic phase and a small amounts of hexagonal phases. The crystallization and the surface pattern of the films were clearly improved with increasing ethylenediamine concentration due to its enhanced complexing role. The absorption edge of the films almost underwent a blue shift with increasing ethylenediamine concentration, which was largely attributed to the quantum confinement effects caused by the small particle size of the polycrystalline ZnS films. Defect species and the corresponding strengths of the ZnS films were strongly affected by the ethylenediamine concentration.

Substitution-inert trinuclear platinum complexes efficiently condense/aggregate nucleic acids and inhibit enzymatic activity**

PubMed Central

Malina, Jaroslav; Farrell, Nicholas P.; Brabec, Viktor

2015-01-01

The trinuclear platinum complexes ([{Pt(NH3)3}2-μ-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}]6+, TriplatinNC‐A; [{trans-Pt(NH3)2(NH2(CH2)6NH3+)}2-μ-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}]8+, TriplatinNC) belong to a class of biologically active agents that bind to DNA via nonbonding noncovalent (hydrogen bonding, electrostatic) interactions. Charge delocalization (6+ to 8+) in these linear trinuclear platinum complexes results in a high cellular uptake and promising cytotoxic activity in several carcinoma cell lines. We show in the present work with the aid of the methods of biophysical chemistry that in particular TriplatinNC condenses DNA with unprecedented potency which is much higher than that of conventional DNA condensing agents. In addition, in contrast to other DNA condensing agents, both platinum complexes induce aggregation of small transfer RNA molecules. We also demonstrate for the first time that TriplatinNC-A and TriplatinNC in particular completely inhibit DNA transcriptional activity at markedly lower concentration than naturally occurring spermine. Notably, the topoisomerase I-mediated relaxation of supercoiled DNA was inhibited by TriplatinNC-A and TriplatinNC at ~60-fold and ~250-fold lower concentration than that of spermine, respectively. We suggest that the general mechanisms of biological activity of TriplatinNC-A and TriplatinNC may be associated with their unique ability to condense/aggregate nucleic acids with consequent inhibitory effect on crucial enzymatic activities. PMID:25256921

Activated Prothrombin Complex Concentrate Versus 4-Factor Prothrombin Complex Concentrate for Vitamin K-Antagonist Reversal.

PubMed

Rowe, A Shaun; Dietrich, Scott K; Phillips, John W; Foster, Kaci E; Canter, Joshua R

2018-06-01

To compare the international normalized ratio normalization efficacy of activated prothrombin complex concentrates and 4-factor prothrombin complex concentrates and to evaluate the thrombotic complications in patients treated with these products for warfarin-associated hemorrhage. Retrospective, Multicenter Cohort. Large, Community, Teaching Hospital. Patients greater than 18 years old and received either activated prothrombin complex concentrate or 4-factor prothrombin complex concentrate for the treatment of warfarin-associated hemorrhage. We excluded those patients who received either agent for an indication other than warfarin-associated hemorrhage, pregnant, had a baseline international normalized ratio of less than 2, received a massive transfusion as defined by hospital protocol, received plasma for treatment of warfarin-associated hemorrhage, or were treated for an acute warfarin ingestion. Patients in the activated prothrombin complex concentrate group (enrolled from one hospital) with an international normalized ratio of less than 5 received 500 IU and those with an international normalized ratio greater than 5 received 1,000 IU. Patients in the 4-factor prothrombin complex concentrate (enrolled from a separate hospital) group received the Food and Drug Administration approved dosing algorithm. A total of 158 patients were included in the final analysis (activated prothrombin complex concentrate = 118; 4-factor prothrombin complex concentrate = 40). Those in the 4-factor prothrombin complex concentrate group had a higher pretreatment international normalized ratio (2.7 ± 1.8 vs 3.5 ± 2.9; p = 0.0164). However, the posttreatment international normalized ratio was similar between the groups. In addition, even when controlling for differences in the pretreatment international normalized ratio, there was no difference in the ability to achieve a posttreatment international normalized ratio of less than 1.4 (odds ratio, 0.753 [95% CI, 0.637-0.890]; p = 0.0009). Those in the activated prothrombin complex concentrate group did have higher odds of achieving a posttreatment international normalized ratio of less than 1.2 (odds ratio, 3.23 [95% CI, 1.34-7.81]; p = 0.0088). There was only one posttreatment thrombotic complication reported. A low, fixed dose of activated prothrombin complex concentrate was as effective as standard dose 4-factor prothrombin complex concentrate for normalization of international normalized ratio. In addition, we did not see an increase in thrombotic events.

Solubility enhancement of seven metal contaminants using carboxymethyl-β-cyclodextrin (CMCD)

NASA Astrophysics Data System (ADS)

Skold, Magnus E.; Thyne, Geoffrey D.; Drexler, John W.; McCray, John E.

2009-07-01

Carboxymethyl-β-cyclodextrin (CMCD) has been suggested as a complexing agent for remediation of sites co-contaminated with metals and organic pollutants. As part of an attempt to construct a geochemical complexation model for metal-CMCD interactions, conditional formation constants for the complexes between CMCD and 7 metal ions (Ba, Ca, Cd, Ni, Pb, Sr, and Zn) are estimated from experimental data. Stable metal concentrations were reached after approximately 1 day and estimated logarithmic conditional formation constants range from - 3.2 to - 5.1 with confidence intervals within ± 0.08 log units. Experiments performed at 10 °C and 25 °C show that temperature affects the solubility of the metal salts but the strength of CMCD-metal complexes are not affected by this temperature variation. The conditional stability constants and complexation model presented in this work can be used to screen CMCD as a potential remediation agent for clean-up of contaminated soil and groundwater.

Ferrimagnetic susceptibility contrast agents.

PubMed

Bach-Gansmo, T

1993-01-01

Contrast agents based on superparamagnetic particles have been in clinical development for more than 5 years, and the complexity of their effects is still not elucidated. The relaxivities are frequently used to give an idea of their efficacy, but these parameters can only be used if they are concentration independent. For large superparamagnetic systems, the evolution of the transverse magnetization is biexponential, after an initial loss of magnetization. Both these characteristics of large superparamagnetic systems should lead to prudence in using the relaxivities as indicators of contrast medium efficacy. Susceptibility induced artefacts have been associated with the use of superparamagnetic contrast agents since the first imaging evaluation took place. The range of concentrations where good contrast effect was achieved without inducing artefacts, as well as blurring and metal artefacts were evaluated. The influence of motion on the induction of artefacts was studied, and compared to the artefacts induced by a paramagnetic agent subject to motion. With a suitable concentration of a negative contrast agent, a signal void could be achieved in the region prone to motion, and no artefacts were induced. If the concentration was too high, a displacement of the region close to the contrast agent was observed. The artefacts occurred in a volume surrounding the contrast agent, i.e., also outside the imaging plane. In comparison a positive, paramagnetic contrast agent induced heavy artefacts in the phase encoding direction, appearing as both high intensity regions and black holes, in a mosaic pattern. Clinical trials of the oral contrast agent OMP for abdominal MR imaging showed this agent to be safe and efficacious. OMP increased the diagnostic efficacy of abdominal MR imaging in 2 of 3 cases examined, with a significant decrease in motion artefacts. Susceptibility contrast agents may also be of use in the evaluation of small lesions in the liver. Particulate material injected i.v. will be targeted to the liver and spleen by way of the mononuclear phagocyte system (MPS). Small particles, without specific receptor affinities were targeted to the hepatocytes and the MPS. The distribution correlated with a high efficiency as a contrast agent, whereas no correlation to in vitro relaxation rates and relaxivities could be found. Superparamagnetic particles have important possibilities as contrast agents. The identification of in vitro properties of these agents may help the comparison of various agents before in vivo imaging.

Headgroup interactions and ion flotation efficiency in mixtures of a chelating surfactant, different foaming agents, and divalent metal ions.

PubMed

Svanedal, Ida; Boija, Susanne; Norgren, Magnus; Edlund, Håkan

2014-06-10

The correlation between interaction parameters and ion flotation efficiency in mixtures of chelating surfactant metal complexes and different foaming agents was investigated. We have recently shown that chelating surfactant 2-dodecyldiethylenetriaminepentaacetic acid (4-C12-DTPA) forms strong coordination complexes with divalent metal ions, and this can be utilized in ion flotation. Interaction parameters for mixed micelles and mixed monolayer formation for Mg(2+) and Ni(2+) complexes with the chelating surfactant 4-C12-DTPA and different foaming agents were calculated by Rubingh's regular solution theory. Parameters for the calculations were extracted from surface tension measurements and NMR diffusometry. The effects of metal ion coordination on the interactions between 4-C12-DTPA and the foaming agents could be linked to a previously established difference in coordination chemistry between the examined metal ions. As can be expected from mixtures of amphoteric surfactants, the interactions were strongly pH-dependent. Strong correlation was found between interaction parameter β(σ) for mixed monolayer formation and the phase-transfer efficiency of Ni(2+) complexes with 4-C12-DTPA during flotation in a customized flotation cell. In a mixture of Cu(2+) and Zn(2+), the significant difference in conditional stability constants (log K) between the metal complexes was utilized to selectively recover the metal complex with the highest log K (Cu(2+)) by ion flotation. Flotation experiments in an excess concentration of metal ions confirmed the coordination of more than one metal ion to the headgroup of 4-C12-DTPA.

In vitro molecular magnetic resonance imaging detection and measurement of apoptosis using superparamagnetic iron oxide + antibody as ligands for nucleosomes

NASA Astrophysics Data System (ADS)

Rapley, P. L.; Witiw, C.; Rich, K.; Niccoli, S.; Tassotto, M. L.; Th'ng, J.

2012-11-01

Recent research in cell biology as well as oncology research has focused on apoptosis or programmed cell death as a means of quantifying the induced effects of treatment. A hallmark of late-stage apoptosis is nuclear fragmentation in which DNA is degraded to release nucleosomes with their associated histones. In this work, a method was developed for detecting and measuring nucleosome concentration in vitro with magnetic resonance imaging (MRI). The indirect procedure used a commercially available secondary antibody-superparamagnetic iron oxide (SPIO) particle complex as a contrast agent that bound to primary antibodies against nucleosomal histones H4, H2A and H2B. Using a multiple-echo spin-echo sequence on a 1.5 T clinical MRI scanner, significant T2 relaxation enhancement as a function of in vitro nucleosomal concentration was measured. In addition, clustering or aggregation of the contrast agent was demonstrated with its associated enhancement in T2 effects. The T2 clustering enhancement showed a complex dependence on relative concentrations of nucleosomes, primary antibody and secondary antibody + SPIO. The technique supports the feasibility of using MRI measurements of nucleosome concentration in blood as a diagnostic, prognostic and predictive tool in the management of cancer.

Secondary electrospray ionization of complex vapor mixtures. Theoretical and experimental approach.

PubMed

Vidal-de-Miguel, Guillermo; Herrero, Ana

2012-06-01

In secondary electrospray ionization (SESI) systems, gaseous analytes exposed to an electrospray plume become ionized after charge is transferred from the charging electrosprayed particles (the charging agent) to the vapor species. Currently available SESI models are valid for simplified systems having only one type of electrosprayed species, which ionizes only one single vapor species, and for the limit of low vapor concentration. More realistic models require considering other effects. Here we develop a theoretical model that accounts for the effects of high vapor concentration, saturation effects, interferences between different vapor species, and electrosprays producing different types of species from the liquid phase. In spite of the relatively high complexity of the problem, we find simple relations between the different ionic species concentrations that hold independently of the particular ion source configuration. Our model suggests that an ideal SESI system should use highly concentrated charging agents composed preferably of only one dominating species with low mobility. Experimental measurements with a MeOH-H(2)O-NH(3) electrospray and a mixture of fatty acids and lactic acid served to test the theory, which gives good qualitative results. These results also suggest that the SESI ionization mechanism is primarily based on ions rather than on charged droplets.

Synthesis and characterization of lead sulphide thin films from ethanolamine (ETA) complexing agent chemical bath

NASA Astrophysics Data System (ADS)

Gashaw Hone, Fekadu; Dejene, F. B.

2018-02-01

Polycrystalline lead sulphide (PbS) thin films were grown on glass substrates by chemical bath deposition route using ethanolamine (ETA) as a complexing agent. The effects of ETA molar concentration on the structural, morphological, electrical and optical properties of lead sulphide thin films were thoroughly studied. The XRD analyses revealed that all the deposited thin films were face center cubic crystal structure and their preferred orientations were varied along the (111) and (200) planes. The XRD results further confirmed that ETA concentration had a significant effects on the strain, average crystalline size and dislocation density of the deposited thin films. The SEM studies illustrated the evolution and transformation of surface morphology as ETA molar concentration increased from 0.41 M to 1.64 M. The energy dispersive x-ray analysis was used to verify the compositional elements of the deposited thin films. Optical spectroscopy investigation established that the band gap of the PbS thin films were reduced from 0.98 eV to 0.68 eV as ETA concentration increased. The photoluminescence spectra showed a well defined peak at 428 nm and shoulder around 468 nm for all PbS thin films. The electrical resistivity of the thin films found in the order of 103 Ω cm at room temperature and decreased as the ETA molar concentration was increased.

Concentration of clarithromycin and 14-R-hydroxy-clarithromycin in plasma of patients with Mycobacterium avium complex infection, before and after the addition of rifampicin.

PubMed

Yamamoto, F; Harada, S; Mitsuyama, T; Harada, Y; Kitahara, Y; Yoshida, M; Nakanishi, Y

2004-02-01

Clarithromycin (CAM) and rifampicin (RFP) have both been recognized to be effective antibiotic agents against Mycobacterium avium complex (MAC) infection. Rifamycin derivatives including RFP and rifabutin modulate the CAM metabolism by inducing the hepatic cytochrome p-450 3A4. To clarify the effect of RFP on the CAM metabolism, we measured the plasma concentration of CAM and 14-R-hydroxyclarithromycin (M-5), the major metabolite of CAM, in 9 patients suffering from MAC infection before and after the addition of RFP. After the addition of RFP, the mean plasma concentration of CAM significantly decreased, while that of M-5 did not. In addition, the amount of CAM + M-5 concentration also significantly decreased. As M-5 is less effective against MAC infection than CAM, more attention should thus be paid to the plasma CAM concentration in patients administered CAM and RFP concomitantly.

Time-Resolved Laser Fluorescence Spectroscopy Study of the Coordination Chemistry of a Hydrophilic CHON [1,2,3-Triazol-4-yl]pyridine Ligand with Cm(III) and Eu(III).

PubMed

Wagner, Christoph; Mossini, Eros; Macerata, Elena; Mariani, Mario; Arduini, Arturo; Casnati, Alessandro; Geist, Andreas; Panak, Petra J

2017-02-20

The complexation of Cm(III) and Eu(III) with the novel i-SANEX complexing agent 2,6-bis[1-(propan-1-ol)-1,2,3-triazol-4-yl]pyridine (PTD) was studied by time-resolved laser fluorescence spectroscopy (TRLFS). The formation of 1:3, 1:2, and 1:1 metal/ligand complexes was identified upon increasing PTD concentration in 10 -3 mol/L HClO 4 and in 0.44 mol/L HNO 3 solutions. For all these complexes, stability constants were determined at different acid concentrations. Though under the extraction conditions proposed for an An/Ln separation process, that is, for 0.08 mol/L PTD in 0.44 mol/L HNO 3 , 1:3 complexes represent the major species, a significant fraction of 1:2 complexes was found. This is caused by ligand protonation, and results in lower Eu(III)/Am(III) separation factors compared to SO 3 -Ph-BTP, until now considered the i-SANEX reference ligand. Focused extraction studies performed at lower proton concentration, where the 1:3 complex is formed exclusively, confirm this assumption.

Substitution-inert trinuclear platinum complexes efficiently condense/aggregate nucleic acids and inhibit enzymatic activity.

PubMed

Malina, Jaroslav; Farrell, Nicholas P; Brabec, Viktor

2014-11-17

The trinuclear platinum complexes (TriplatinNC-A [{Pt(NH3 )3 }2 -μ-{trans-Pt(NH3 )2 (NH2 (CH2 )6 NH2 )2 }](6+) , and TriplatinNC [{trans-Pt(NH3 )2 (NH2 (CH2 )6 NH3 (+) )}2 -μ-{trans-Pt(NH3 )2 (NH2 (CH2 )6 NH2 )2 }](8+) ) are biologically active agents that bind to DNA through noncovalent (hydrogen bonding, electrostatic) interactions. Herein, we show that TriplatinNC condenses DNA with a much higher potency than conventional DNA condensing agents. Both complexes induce aggregation of small transfer RNA molecules, and TriplatinNC in particular completely inhibits DNA transcription at lower concentrations than naturally occurring spermine. Topoisomerase I-mediated relaxation of supercoiled DNA was inhibited by TriplatinNC-A and TriplatinNC at concentrations which were 60 times and 250 times lower than that of spermine. The mechanisms for the biological activity of TriplatinNC-A and TriplatinNC may be associated with their ability to condense/aggregate nucleic acids with consequent inhibitory effects on crucial enzymatic activities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Designing novel cellulase systems through agent-based modeling and global sensitivity analysis.

PubMed

Apte, Advait A; Senger, Ryan S; Fong, Stephen S

2014-01-01

Experimental techniques allow engineering of biological systems to modify functionality; however, there still remains a need to develop tools to prioritize targets for modification. In this study, agent-based modeling (ABM) was used to build stochastic models of complexed and non-complexed cellulose hydrolysis, including enzymatic mechanisms for endoglucanase, exoglucanase, and β-glucosidase activity. Modeling results were consistent with experimental observations of higher efficiency in complexed systems than non-complexed systems and established relationships between specific cellulolytic mechanisms and overall efficiency. Global sensitivity analysis (GSA) of model results identified key parameters for improving overall cellulose hydrolysis efficiency including: (1) the cellulase half-life, (2) the exoglucanase activity, and (3) the cellulase composition. Overall, the following parameters were found to significantly influence cellulose consumption in a consolidated bioprocess (CBP): (1) the glucose uptake rate of the culture, (2) the bacterial cell concentration, and (3) the nature of the cellulase enzyme system (complexed or non-complexed). Broadly, these results demonstrate the utility of combining modeling and sensitivity analysis to identify key parameters and/or targets for experimental improvement.

Designing novel cellulase systems through agent-based modeling and global sensitivity analysis

PubMed Central

Apte, Advait A; Senger, Ryan S; Fong, Stephen S

2014-01-01

Experimental techniques allow engineering of biological systems to modify functionality; however, there still remains a need to develop tools to prioritize targets for modification. In this study, agent-based modeling (ABM) was used to build stochastic models of complexed and non-complexed cellulose hydrolysis, including enzymatic mechanisms for endoglucanase, exoglucanase, and β-glucosidase activity. Modeling results were consistent with experimental observations of higher efficiency in complexed systems than non-complexed systems and established relationships between specific cellulolytic mechanisms and overall efficiency. Global sensitivity analysis (GSA) of model results identified key parameters for improving overall cellulose hydrolysis efficiency including: (1) the cellulase half-life, (2) the exoglucanase activity, and (3) the cellulase composition. Overall, the following parameters were found to significantly influence cellulose consumption in a consolidated bioprocess (CBP): (1) the glucose uptake rate of the culture, (2) the bacterial cell concentration, and (3) the nature of the cellulase enzyme system (complexed or non-complexed). Broadly, these results demonstrate the utility of combining modeling and sensitivity analysis to identify key parameters and/or targets for experimental improvement. PMID:24830736

Environmentally relevant concentrations of aminopolycarboxylate chelating agents mobilize Cd from humic acid.

PubMed

North, Ashley E; Sarpong-Kumankomah, Sophia; Bellavie, Andrew R; White, Wade M; Gailer, Jürgen

2017-07-01

Although Cd is a pollutant of public health relevance, many dietary sources from which it can be absorbed into human tissues remain unknown. While it is well established that the biogeochemical cycle of Cd involves its complexation with environment-derived ligands (e.g., humic acids, HAs) and anthropogenic ones (e.g., chelating agents, CAs), the interaction of Cd with both of these ligands is less well understood. To gain insight, a HA-Cd complex was injected on a size-exclusion chromatography (SEC) column coupled on-line with a flame atomic absorption spectrometer (FAAS) using 10mmol/L Tris buffer (pH8.0) as the mobile phase. This approach allowed us to observe the intact HA-Cd complex and the retention behavior of Cd as a function of 2-20μmol/L concentrations of ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) or methylglycinediacetic acid (MGDA) that were added to the mobile phase. An increase of the retention time of Cd was indicative of a partial or complete abstraction of Cd from HA. Our results revealed that all CAs abstracted Cd from the HA-Cd complex at concentrations of 5μmol/L, while MGDA and DTPA were effective at 2μmol/L. The bioavailability of some of the on-column formed CA-Cd complexes explains the previously reported increased accumulation of Cd in periphyton in the ecosystem downstream of wastewater treatment plants. In addition, our results imply that the use of effluents which contain CAs and Cd for the irrigation of food crops can introduce Cd into the food supply and compromise food safety. Copyright © 2017. Published by Elsevier B.V.

Superparamagnetic And Paramagnetic MRI Contrast Agents: Application Of Rapid Magnetic Resonance Imaging To Assess Renal Function

NASA Astrophysics Data System (ADS)

Carvlin, Mark J.; Renshaw, Perry F.; Arger, Peter; Kundel, Harold L.; Dougherty, Larry; Axel, Leon; Kassab, Eleanor; Moore, Bethanne

1988-06-01

The paramagnetic chelate complex, gadolinium-diethylene-triamine-pentaacetic acid, Gd-DTPA, and superparamagnetic particles, such as those composed of dextran coated magnetite, function as magnetic resonance contrast agents by changing the relaxation rates, 1/T1 and 1/T2. The effects that these agents have upon MR signal intensity are determined by: the inherent biophysical properties of the tissue being imaged, the concentration of the contrast agent and the data acquisition scheme (pulse sequence parameters) employed. Following the time course of MR signal change in the first minutes after the injection of contrast agent(s) allows a dynamic assessment of organ functions in a manner analogous to certain nuclear medicine studies. In order to study renal function, sequential MR fast scan images, gradient echo (TR=35/TE=7 msec, flip angle=25 degrees), were acquired, one every 12 seconds, after intravenous injection of Gd-DTPA and/or dextran-magnetite. Gd-DTPA, which is freely filtered at the glomerulus and is neither secreted nor reabsorbed, provides information concerning renal perfusion, glomerular filtration and tubular concentrating ability. Dextran-magnetite (200 A diameter), which is primarily contained within the intravascular space shortly after injection, provides information on blood flow to and distribution within the kidney. The MR signal change observed after administration of contrast agents varied dramatically depending upon the agents injected and the imaging parameters used. Hence a broad range of physiolgic processes may be described using these techniques, i.e. contrast agent enhanced functional MR examinations.

Molecular nanomagnets as contrast agents for Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Rodríguez, Elisenda; Roig, Anna; Molins, Elies; Arús, Carles; Cabañas, Miquel; Quintero, María Rosa; Cerdán, Sebastián; Sanfeliu, Coral

2003-03-01

Magnetic resonance imaging (MRI) is a non-invasive technique used in medicine to produce high quality images of human body slices. In order to enhance the contrast between different organs or to reveal altered portions of them such necrosis or tumors, the administration of a contrast agent is highly convenient. Currently Gd-DTPA, a paramagnetic complex, is the most widely administered compound. In this context, we have assayed molecular nanomagnets as MRI contrast agents. The complex [(tacn)_6Fe_8(μ_3-O)_2(μ_2-OH)_12]Br_8·9H_2O^1(Fe8 in brief) has been evaluated and shorter relaxation times, T1 and T_2, have been obtained for Fe8 than those obtained for the commercial Gd-DTPA. No toxic effects have been observed at concentrations up to 1 mM of Fe8 in cultured cells. Phantom studies with T_1-weighted MRI at 9.4 Tesla suggest that Fe8 can have potentiality as T_1-contrast agent. ^1Wieghardt K Angew Chem Intl Ed Engl 23 1 (1984) 77

Effects of sub-minimum inhibitory concentrations of antimicrobial agents on Streptococcus mutans biofilm formation.

PubMed

Dong, Liping; Tong, Zhongchun; Linghu, Dake; Lin, Yuan; Tao, Rui; Liu, Jun; Tian, Yu; Ni, Longxing

2012-05-01

Many studies have demonstrated that sub-minimum inhibitory concentrations (sub-MICs) of antimicrobial agents can inhibit bacterial biofilm formation. However, the mechanisms by which antimicrobial agents at sub-MICs inhibit biofilm formation remain unclear. At present, most studies are focused on Gram-negative bacteria; however, the effects of sub-MICs of antimicrobial agents on Gram-positive bacteria may be more complex. Streptococcus mutans is a major cariogenic bacterium. In this study, the S. mutans growth curve as well as the expression of genes related to S. mutans biofilm formation were evaluated following treatment with 0.5× MIC of chlorhexidine (CHX), tea polyphenols and sodium fluoride (NaF), which are common anticaries agents. The BioFlux system was employed to generate a biofilm under a controlled flow. Morphological changes of the S. mutans biofilm were observed and analysed using field emission scanning electron microscopy and confocal laser scanning microscopy. The results indicated that these three common anticaries agents could significantly upregulate expression of the genes related to S. mutans biofilm formation, and S. mutans exhibited a dense biofilm with an extensive extracellular matrix following treatment with sub-MICs of NaF and CHX. These findings suggest that sub-MICs of anticaries agents favour S. mutans biofilm formation, which might encourage dental caries progression. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Interactions of platinum metals and their complexes in biological systems.

PubMed Central

LeRoy, A F

1975-01-01

Platinum-metal oxidation catalysts are to be introduced in exhaust systems of many 1975 model-year automobiles in the U.S. to meet Clean Air Act standards. Small quantities of finely divided catalyst have been found issuing from prototype systems; platinum and palladium compounds may be found also. Although platinum exhibits a remarkable resistance to oxidation and chemical attack, it reacts chemically under some conditions producing coordination complex compounds. Palladium reacts more readily than platinum. Some platinum-metal complexes interact with biological systems as bacteriostatic, bacteriocidal, viricidal, and immunosuppressive agents. Workers chronically exposed to platinum complexes often develop asthma-like respiratory distress and skin reactions called platinosis. Platinum complexes used alone and in combination therapy with other drugs have recently emerged as effective agents in cancer chemotherapy. Understanding toxic and favorable interactions of metal species with living organisms requires basic information on quantities and chemical characteristics of complexes at trace concentrations in biological materials. Some basic chemical kinetic and thermodynamic data are presented to characterize the chemical behavior of the complex cis-[Pt(NH3)2Cl2] used therapeutically. A brief discussion of platinum at manogram levels in biological tissue is discussed. PMID:50943

The importance of ligand speciation in environmental research: a case study.

PubMed

Sillanpää, M; Orama, M; Rämö, J; Oikari, A

2001-02-21

The speciations of EDTA and DTPA in process, waste and river waters are modelled and simulated, specifically to the mode of occurrence in the pulp and paper mill effluents and subsequently in receiving waters. Due to relatively short residence times in bleaching process and waste water treatment and slow exchange kinetics, it is expected that the thermodynamic equilibrium is not necessarily reached. Therefore, the initial speciation plays a key role. As such, the simulations have been extended to the process waters of the pulp and paper industry taking into account estimated average conditions. The results reveal that the main species are; Mn and Ca complexes of EDTA and DTPA in pulp mill process waters; Fe(III) and Mn complexes of EDTA and DTPA in waste waters; Fe(III) and Zn complexes of EDTA and DTPA in receiving waters. It is also shown how the increasing concentration of complexing agents effects the speciation. Alkaline earth metal chelation plays a significant role in the speciation of EDTA and DTPA when there is a noticeable molar excess of complexing agents compared with transition metals.

Virtual exploration of early stage atherosclerosis.

PubMed

Olivares, Andy L; González Ballester, Miguel A; Noailly, Jérôme

2016-12-15

Biological mechanisms contributing to atherogenesis are multiple and complex. The early stage of atherosclerosis (AS) is characterized by the accumulation of low-density lipoprotein (LDL) droplets, leading to the creation of foam cells (FC). To address the difficulty to explore the dynamics of interactions that controls this process, this study aimed to develop a model of agents and infer on the most influential cell- and molecule-related parameters. FC started to accumulate after six to eight months of simulated hypercholesterolemia. A sensitivity analysis revealed the strong influence of LDL oxidation rate on the risk of FC creation, which was exploited to model the antioxidant effect of statins. Combined with an empirical simulation of the drug ability to decrease the level of LDL, the virtual statins treatment led to reductions of oxidized LDL levels similar to reductions measured in vivo. An Open source software was used to develop the agent-based model of early AS. Two different concentrations of LDL agents were imposed in the intima layer to simulate healthy and hypercholesterolemia groups of 'virtual patients'. The interactions programmed between molecules and cells were based on experiments and models reported in the literature. A factorial sensitivity analysis explored the respective effects of the less documented model parameters as (i) agent migration speed, (ii) LDL oxidation rate and (iii) concentration of autoantibody agents. Finally, the response of the model to known perturbations was assessed by introducing statins agents, able to reduce the oxidation rate of LDL agents and the LDL boundary concentrations. jerome.noailly@upf.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Considerations in detecting CDC select agents under field conditions

NASA Astrophysics Data System (ADS)

Spinelli, Charles; Soelberg, Scott; Swanson, Nathaneal; Furlong, Clement; Baker, Paul

2008-04-01

Surface Plasmon Resonance (SPR) has become a widely accepted technique for real-time detection of interactions between receptor molecules and ligands. Antibody may serve as receptor and can be attached to the gold surface of the SPR device, while candidate analyte fluids contact the detecting antibody. Minute, but detectable, changes in refractive indices (RI) indicate that analyte has bound to the antibody. A decade ago, an inexpensive, robust, miniature and fully integrated SPR chip, called SPREETA, was developed. University of Washington (UW) researchers subsequently developed a portable, temperature-regulated instrument, called SPIRIT, to simultaneously use eight of these three-channel SPREETA chips. A SPIRIT prototype instrument was tested in the field, coupled to a remote reporting system on a surrogate unmanned aerial vehicle (UAV). Two target protein analytes were released sequentially as aerosols with low analyte concentration during each of three flights and were successfully detected and verified. Laboratory experimentation with a more advanced SPIRIT instrument demonstrated detection of very low levels of several select biological agents that might be employed by bioterrorists. Agent detection under field-like conditions is more challenging, especially as analyte concentrations are reduced and complex matricies are introduced. Two different sample preconditioning protocols have been developed for select agents in complex matrices. Use of these preconditioning techniques has allowed laboratory detection in spiked heavy mud of Francisella tularensis at 10 3 CFU/ml, Bacillus anthracis spores at 10 3 CFU/ml, Staphylococcal enterotoxin B (SEB) at 1 ng/ml, and Vaccinia virus (a smallpox simulant) at 10 5 PFU/ml. Ongoing experiments are aimed at simultaneous detection of multiple agents in spiked heavy mud, using a multiplex preconditioning protocol.

Grounding language in action and perception: From cognitive agents to humanoid robots

NASA Astrophysics Data System (ADS)

Cangelosi, Angelo

2010-06-01

In this review we concentrate on a grounded approach to the modeling of cognition through the methodologies of cognitive agents and developmental robotics. This work will focus on the modeling of the evolutionary and developmental acquisition of linguistic capabilities based on the principles of symbol grounding. We review cognitive agent and developmental robotics models of the grounding of language to demonstrate their consistency with the empirical and theoretical evidence on language grounding and embodiment, and to reveal the benefits of such an approach in the design of linguistic capabilities in cognitive robotic agents. In particular, three different models will be discussed, where the complexity of the agent's sensorimotor and cognitive system gradually increases: from a multi-agent simulation of language evolution, to a simulated robotic agent model for symbol grounding transfer, to a model of language comprehension in the humanoid robot iCub. The review also discusses the benefits of the use of humanoid robotic platform, and specifically of the open source iCub platform, for the study of embodied cognition.

Relevance of liver failure for anti-infective agents: from pharmacokinetic alterations to dosage adjustments

PubMed Central

Büdingen, Fiona V.; Gonzalez, Daniel; Tucker, Amelia N.

2014-01-01

The liver is a complex organ with great ability to influence drug pharmacokinetics (PK). Due to its wide array of function, its impairment has the potential to affect bioavailability, enterohepatic circulation, drug distribution, metabolism, clearance, and biliary elimination. These alterations differ widely depending on the cause of the liver failure, if it is acute or chronic in nature, the extent of impairment, and comorbid conditions. In addition, the effects on liver functions do not occur in a proportional or predictable manner for escalating degrees of liver impairment. The ability of hepatic alterations to influence PK is also dependent on drug characteristics, such as administration route, chemical properties, protein binding, and extraction ratio, among others. This complexity makes it difficult to predict what effects these changes will have on a particular drug. Unlike certain classes of agents, efficacy of anti-infectives is most often dependent on fulfilling PK/pharmacodynamic targets, such as maximum concentration/minimum inhibitory concentration (Cmax/MIC), area under the curve/minimum inhibitory concentration (AUC/MIC), time above MIC (T>MIC), half-maximal inhibitory concentration (IC50) or half-maximal effective concentration (EC50), or the time above the concentration which inhibits viral replication by 95% (T>EC95). Loss of efficacy and/or an increased risk of toxicity may occur in certain circumstances of liver injury. Although it is important to consider these potential alterations and their effects on specific anti-infectives, many lack data to constitute specific dosing adjustments, making it important to monitor patients for effectiveness and toxicities of therapy. PMID:24949199

Hemophilia and von Willebrand's disease: 2. Management. Association of Hemophilia Clinic Directors of Canada.

PubMed Central

1995-01-01

OBJECTIVE: To present current strategies for the treatment of hemophilia and von Willebrand's disease. OPTIONS: Prophylactic and corrective therapy with hemostatic and adjunctive agents: DDAVP (1-desamino-8-D-arginine vasopressin [desmopressin acetate]), recombinant coagulation products (human Factor VIII and human Factor VIIa) or virally inactivated plasma-derived products (high- or ultra-high-purity human Factor VIII or human Factor VIII concentrate containing von Willebrand factor activity, porcine Factor VIII, high-purity human Factor IX, human prothrombin-complex concentrate, human activated prothrombin-complex concentrate), adjunctive antifibrinolytic agents, topical thrombin and fibrin sealant. The induction of immune tolerance in patients in whom inhibitors develop should also be considered. OUTCOMES: Morbidity and quality of life associated with bleeding and treatment. EVIDENCE: Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of our reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and pertinent to a predetermined outline. The availability of treatment products in Canada was also considered. VALUES: Minimizing morbidity and maximizing functional status and quality of life were given a high value. BENEFITS, HARMS AND COSTS: Proper prophylactic or early treatment with appropriate hemostatic agents minimizes morbidity and functional disability and improves quality of life. Economic gains are realized through the reduction of mortality and morbidity and their associated costs. The patient has a better opportunity to contribute to society through gainful employment and the fulfillment of social roles. Potential harms include HIV infection, hepatitis B, hepatitis C and the development of inhibitor antibodies to clotting-factor concentrates. The risk of viral transmission has been minimized through the development of procedures for the viral inactivation of plasma-derived clotting-factor concentrates and through the use of recombinant coagulation-factor concentrates and other non-plasma-derived hemostatic agents. RECOMMENDATIONS: DDAVP is the drug of choice for patients with mild hemophilia or type 1 or 2 (except 2B) von Willebrand's disease whose response to DDAVP in previous testing has been found to be adequate. Therapeutic blood components of choice include recombinant products and virally inactivated plasma-derived products. In Canada the recommended products are recombinant Factor VIII for hemophilia A, high-purity plasma-derived Factor IX for hemophilia B and plasma-derived Factor VIII concentrates containing adequate von Willebrand factor (e.g., Haemate P) for von Willebrand's disease. Dosages vary according to specific indications. Adjunctive antifibrinolytic agents, topical thrombin and fibrin sealant are useful for the treatment of oral or dental bleeds and localized bleeds in accessible sites. In patients with inhibitor antibodies, high-dose human or porcine Factor VIII is usually effective when the inhibitor titre is less than 5 Bethesda units/mL. In nonresponsive patients, or in those whose inhibitor titre is higher, "bypassing" agents (e.g., activated prothrombin-complex concentrate and recombinant Factor VIIa) are useful. Long-term management may include immune-tolerance induction.VALIDATION: These recommendations were reviewed and approved by the Association of Hemophilia Clinic Directors of Canada (AHCDC) and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society. No similar consensus statements or practice guidelines are available for comparison. SPONSORS: These recommendations were developed at the request of the Canadian Blood Agency, which funds the provision of all coagulation-factor concentrates for people with congenital bleeding disorders, and were developed and endorsed by the AHCDC and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society. PMID:7600466

Anti-Leishmania activity of new ruthenium(II) complexes: Effect on parasite-host interaction.

PubMed

Costa, Mônica S; Gonçalves, Yasmim G; Nunes, Débora C O; Napolitano, Danielle R; Maia, Pedro I S; Rodrigues, Renata S; Rodrigues, Veridiana M; Von Poelhsitz, Gustavo; Yoneyama, Kelly A G

2017-10-01

Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. The many complications presented by the current treatment - including high toxicity, high cost and parasite resistance - make the development of new therapeutic agents indispensable. The present study aims to evaluate the anti-Leishmania potential of new ruthenium(II) complexes, cis‑[Ru II (η 2 -O 2 CR)(dppm) 2 ]PF 6 , with dppm=bis(diphenylphosphino)methane and R=4-butylbenzoate (bbato) 1, 4-(methylthio)benzoate (mtbato) 2 and 3-hydroxy-4-methoxybenzoate (hmxbato) 3, in promastigote cytotoxicity and their effect on parasite-host interaction. The cytotoxicity of complexes was analyzed by MTT assay against Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Leishmania) infantum promastigotes and the murine macrophage (RAW 264.7). The effect of complexes on parasite-host interaction was evaluated by in vitro infectivity assay performed in the presence of two different concentrations of each complex: the promastigote IC 50 value and the concentration nontoxic to 90% of RAW 264.7 macrophages. Complexes 1-3 exhibited potent cytotoxic activity against all Leishmania species assayed. The IC 50 values ranged from 7.52-12.59μM (complex 1); 0.70-3.28μM (complex 2) and 0.52-1.75μM (complex 3). All complexes significantly inhibited the infectivity index at both tested concentrations. The infectivity inhibitions ranged from 37 to 85%. Interestingly, the infectivity inhibitions due to complex action did not differ significantly at either of the tested concentrations, except for the complex 1 against Leishmania (Leishmania) infantum. The infectivity inhibitions resulted from reductions in both percentage of infected macrophages and number of parasites per macrophage. Taken together the results suggest remarkable leishmanicidal activity in vitro by these new ruthenium(II) complexes. Copyright © 2017 Elsevier Inc. All rights reserved.

Myricetin arrests human telomeric G-quadruplex structure: a new mechanistic approach as an anticancer agent.

PubMed

Mondal, Soma; Jana, Jagannath; Sengupta, Pallabi; Jana, Samarjit; Chatterjee, Subhrangsu

2016-07-19

The use of small molecules to arrest G-quadruplex structure has become a potential strategy for the development and design of a new class of anticancer therapeutics. We have studied the interaction of myricetin, a plant flavonoid and a putative anticancer agent, with human telomeric G-quadruplex TTAGGG(TTAGGG)3 DNA. Reverse transcription PCR data revealed significant repression in hTERT expression in MCF-7 breast cancer cells upon increasing the concentration of myricetin. Further, we conducted a telomeric repeat amplification protocol assay to confirm the inhibition of telomerase by myricetin. Optical spectroscopic techniques like circular dichroism, UV spectroscopy and fluorescence spectroscopy revealed the formation of a stable myricetin-G-quadruplex complex. The thermodynamic parameters of myricetin-G-quadruplex complex formation, presented through isothermal titration calorimetry studies, indicate the binding process to be thermodynamically favorable. In addition, high resolution NMR spectroscopy in conjunction with molecular dynamics simulation is employed to provide detailed mechanistic insights into the binding in the myricetin-G-quadruplex complex at the atomic level. Our results thus propose a new mode of action of myricetin as an anticancer agent via arresting telomeric G-quadruplex structure.

DNA interaction studies of new nano metal based anticancer agent: validation by spectroscopic methods

NASA Astrophysics Data System (ADS)

Tabassum, Sartaj; Sharma, Girish Chandra; Arjmand, Farukh; Azam, Ameer

2010-05-01

A new nano dimensional heterobimetallic Cu-Sn containing complex as a potential drug candidate was designed, synthesized and characterized by analytical and spectral methods. The electronic absorption and electron paramagnetic resonance parameters of the complex revealed that the Cu(II) ion exhibits a square pyramidal geometry with the two pyrazole nitrogen atoms, the amine nitrogen atom and the carboxylate oxygen of the phenyl glycine chloride ligand located at the equatorial sites and the coordinated chloride ion occupying an apical position. 119Sn NMR spectral data showed a hexa-coordinated environment around the Sn(IV) metal ion. TEM, AFM and XRD measurements illustrate that the complex could induce the condensation of CT-DNA to a particulate nanostructure. The interaction of the Cu-Sn complex with CT-DNA was investigated by UV-vis absorption and emission spectroscopy, as well as cyclic voltammetric measurements. The results indicated that the complex interacts with DNA through an electrostatic mode of binding with an intrinsic binding constant Kb = 8.42 × 104 M - 1. The Cu-Sn complex exhibits effective cleavage of pBR322 plasmid DNA by an oxidative cleavage mechanism, monitored at different concentrations both in the absence and in the presence of reducing agents.

The crystallogenesis of a human estradiol dehydrogenase-substrate complex

NASA Astrophysics Data System (ADS)

Zhu, Dao-Wei; Azzi, Arezki; Rehse, Peter; Lin, Sheng-Xiang

1996-10-01

Human 17β-hydroxysteroid dehydrogenase type 1 is an important steroidogenic enzyme catalyzing the synthesis of the most active estrogen: estradiol. The enzyme is formed by two identical subunits (34.5 kDa). In this paper, we report the preparation of a stoichiometric 17β-HSD1-estradiol complex sample at a much higher concentration than the solubility of the free substrate, using a gradual concentration of the enzyme-substrate mixture starting at low concentration. The complex is successfully crystallized by vapor diffusion at pH 7.5 with polyethyleneglycol 4000 as the precipitating agent. The space group is C2 with a = 123.56 Å, b = 45.21 Å, c = 61.30 Å and β = 99.06°. There is one monomer in the asymmetric unit and two molecules of the enzyme in a unit cell. A diffraction data set to 2.5 Å has been collected to 86% completeness on native crystals. The high quality of the electronic density map of estradiol supports the full occupancy of the binding site, thus confirming the efficiency of the complex preparation. This method will also be useful in crystallizing other steroid-dehydrogenase complexes.

Pharmacokinetics of Peptide Mediated Delivery of Anticancer Drug Ellipticine

PubMed Central

Pan, Pei; Sadatmousavi, Parisa; Yuan, Yongfang; Chen, P.

2012-01-01

The amino acid pairing peptide EAK16-II (EAK) has shown the ability to stabilize the hydrophobic anticancer agent ellipticine (EPT) in aqueous solution. In this study, we investigate pharmacokinetics of the formulation of EAK-EPT complexes in vivo. The developed formulation can achieve a sufficiently high drug concentration required in vivo animal models. The nanostructure and surface properties of EAK-EPT complexes or nanoparticle were characterized by transmission electron microscopy (TEM) and zeta potential measurements, respectively. 12 healthy male SD rats were divided into EPT group and EAK-EPT group randomly. Rats in EPT group were tail intravenously injected with the EPT (20 mg/kg); rats in EAK-EPT group were injected with EAK-EPT complexes (EPT's concentration is 20 mg/kg). EPT was extracted from rat plasma with dexamethasone sodium phosphate as internal standards (IS). The pharmacokinetic parameters were obtained using high pressure liquid chromatography (HPLC). Significant differences in main pharmacokinetic parameters between EPT and EAK-EPT complexes were observed, demonstrating that the complexation with EAK prolongs the residence time of the drug and enlarges the area under the concentration-time curve (AUC). This means that EAK can serve as a suitable carrier to increase the bioavailability of EPT. PMID:22952737

Polarographic study of cadmium 5-hydroxy 2-(hydroxymethyl) 4H-pyran-4-one complex

NASA Technical Reports Server (NTRS)

Wilson, Ray F.; Daniels, Robert C.

1989-01-01

A polarographic study was performed on the products formed in the interaction of cadmium (II) with a 5-hydroxy 2-(hydroxymethyl) 4H-Pyran-4-one, using varying conditions of pH, supporting electrolytes, and concentrations. Measurements using the differential pulse method show that cadmium (II) exhibits a molar combining ratio of complexing agents to cation ranging from 1 to 1 to 3 to 1 depending on the pH and the supporting electrolyte employed.

Development of a novel, FTIR (Fourier transform infrared spectroscopy) based, yeast bioassay for toxicity testing and stress response study.

PubMed

Corte, Laura; Rellini, Paolo; Roscini, Luca; Fatichenti, Fabrizio; Cardinali, Gianluigi

2010-02-05

Fourier transform infrared spectroscopy (FTIR) was used to analyze the metabolomic alterations caused to yeast cells by four chemical compounds: ethanol, sodium hypochlorite, sodium chloride and sulfur dioxide, each tested at five different concentrations. The complex of four stressing agents at different concentrations, inducing cell mortalities ranging from 1% to 100%, has given the opportunity to prove that FTIR can individuate the presence of a stress before the cells start dying. A series of "Stress Indexes" was calculated with an expressly designed "R" script, to estimate the level of stress induced by the chemical agents at different concentrations. These estimation procedures allowed the direct comparison of the stress induced by the four agents at different concentrations. The response spectra, calculated as difference between the spectrum of the cells under stress and that of the cells maintained in water, showed different shapes in the diverse experimental conditions, suggesting a specificity of the response and the possibility to classify it. The contribution of five different spectral regions (fatty acids, amides, mixed zone, carbohydrates and typing region) could be calculated separately, gaining additional information on the stressing effects. Spectral alterations were detected at concentrations as low as 10% ethanol, 20 ppm bleach, 1 M NaCl and 100 mg L(-1) SO(2). These preliminary findings suggest that FTIR technology and a series of simple algorithms can be employed to study response of cells to various stressing situations, not limited to chemical agents. The ease and rapidity of the FTIR analysis suggest that this approach could be used as a bioassay in several applications and particularly in ecotoxicology and in environmental microbiology. Copyright 2009 Elsevier B.V. All rights reserved.

A Schiff base-derived copper (II) complex is a potent inducer of apoptosis in colon cancer cells by activating the intrinsic pathway.

PubMed

Hajrezaie, Maryam; Paydar, Mohammadjavad; Moghadamtousi, Soheil Zorofchian; Hassandarvish, Pouya; Gwaram, Nura Suleiman; Zahedifard, Maryam; Rouhollahi, Elham; Karimian, Hamed; Looi, Chung Yeng; Ali, Hapipah Mohd; Abdul Majid, Nazia; Abdulla, Mahmood Ameen

2014-01-01

Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87  μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25  μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.

A Schiff Base-Derived Copper (II) Complex Is a Potent Inducer of Apoptosis in Colon Cancer Cells by Activating the Intrinsic Pathway

PubMed Central

Hajrezaie, Maryam; Paydar, Mohammadjavad; Zorofchian Moghadamtousi, Soheil; Hassandarvish, Pouya; Gwaram, Nura Suleiman; Zahedifard, Maryam; Rouhollahi, Elham; Karimian, Hamed; Looi, Chung Yeng; Ali, Hapipah Mohd; Abdul Majid, Nazia; Abdulla, Mahmood Ameen

2014-01-01

Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87 μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25 μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents. PMID:24737979

(+)-3-( sup 123 I)Iodo-MK-801: Synthesis and characterization of binding to the N-methyl-D-aspartate receptor complex

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

Ransom, R.W.; Wai-si Eng; Burns, H.D.

1990-01-01

Synthetic methods have been established for preparing high specific activity (+)-3-({sup 123}I)Iodo-MK-801 in high radiochemical yield. The binding of the radiotracer to rat cortical membranes has been examine to assess its potential use as an in vivo imaging agent for the N-methyl-D-aspartate (NMDA) receptor-ion channel complex. Under the conditions of the assay, specific (+)-3-({sup 123}I)Iodo-MK-801 binding to membrane homogenates represented greater than 95% of the total binding. Several structurally distinct, noncompetitive NMDA receptor antagonists inhibited binding with potencies in accordance with their reported inhibitory activity at the receptor complex. The concentration of ({plus minus})-3-Iodo-MK-801 required to inhibit 50% of (+)-3-({supmore » 123}I)Iodo-MK-801 binding (IC{sub 50}) was 3.4 nM when using a low ionic strength assay buffer and 5.5 nM in a physiological buffer. In a thoroughly washed membrane preparation, (+)-3-({sup 123}I)Iodo-MK-801 binding was enhanced by L-glutamate and glycine at concentrations known to activate the NMDA receptor. The results indicate that (+)-3-({sup 123}I)Iodo-MK-801 specifically labels the NMDA receptor complex in rat brain membranes and the retention of high affinity under near physiological assay conditions suggests that it may be useful as a SPECT imaging agent for the receptor in vivo.« less

Application of High-Resolution Magic-Angle Spinning NMR Spectroscopy to Define the Cell Uptake of MRI Contrast Agents

NASA Astrophysics Data System (ADS)

Calabi, Luisella; Alfieri, Goffredo; Biondi, Luca; De Miranda, Mario; Paleari, Lino; Ghelli, Stefano

2002-06-01

A new method, based on proton high-resolution magic-angle spinning ( 1H HR-MAS) NMR spectroscopy, has been employed to study the cell uptake of magnetic resonance imaging contrast agents (MRI-CAs). The method was tested on human red blood cells (HRBC) and white blood cells (HWBC) by using three gadolinium complexes, widely used in diagnostics, Gd-BOPTA, Gd-DTPA, and Gd-DOTA, and the analogous complexes obtained by replacing Gd(III) with Dy(III), Nd(III), and Tb(III) (i.e., complexes isostructural to the ones of gadolinium but acting as shift agents). The method is based on the evaluation of the magnetic effects, line broadening, or induced lanthanide shift (LIS) caused by these complexes on NMR signals of intra- and extracellular water. Since magnetic effects are directly linked to permeability, this method is direct. In all the tests, these magnetic effects were detected for the extracellular water signal only, providing a direct proof that these complexes are not able to cross the cell membrane. Line broadening effects (i.e., the use of gadolinium complexes) only allow qualitative evaluations. On the contrary, LIS effects can be measured with high precision and they can be related to the concentration of the paramagnetic species in the cellular compartments. This is possible because the HR-MAS technique provides the complete elimination of bulk magnetic susceptibility (BMS) shift and the differentiation of extra- and intracellular water signals. Thus with this method, the rapid quantification of the MRI-CA amount inside and outside the cells is actually feasible.

Biofilms in vitro and in vivo: do singular mechanisms imply cross-resistance?

PubMed

Gilbert, P; Allison, D G; McBain, A J

2002-01-01

Microbial biofilm has become inexorably linked with man's failure to control them by antibiotic and biocide regimes that are effective against suspended bacteria. This failure relates to a localized concentration of biofilm bacteria, and their extracellular products (exopolymers and extracellular enzymes), that moderates the access of the treatment agent and starves the more deeply placed cells. Biofilms, therefore, typically present gradients of physiology and concentration for the imposed treatment agent, which enables the less susceptible clones to survive. Such clones might include efflux mutants in addition to genotypes with modifications in single gene products. Clonal expansion following subeffective treatment would, in the case of many antibiotics, lead to the emergence of a resistant population. This tends not to occur for biocidal treatments where the active agent exhibits multiple pharmacological activity towards a number of specific cellular targets. Whilst resistance development towards biocidal agents is highly unlikely, subeffective exposure will lead to the selection of less susceptible clones, modified either in efflux or in their most susceptible target. The latter might also confer resistance to antibiotics where the target is shared. Thus, recent reports have demonstrated that sublethal concentrations of the antibacterial and antifungal agent triclosan can select for resistant mutants in Escherichia coli and that this agent specifically targets the enzyme enoyl reductase that is involved in lipid biosynthesis. Triclosan may, therefore, select for mutants in a target that is shared with the anti-E. coli diazaborine compounds and the antituberculosis drug isoniazid. Although triclosan may be a uniquely specific biocide, sublethal concentrations of less specific antimicrobial agents may also select for mutations within their most sensitive targets, some of which might be common to therapeutic agents. Sublethal treatment with chemical antimicrobial agents has also been demonstrated to induce the expression of multidrug efflux pumps and efflux mutants. Whilst efflux does not confer protection against use concentrations of biocidal products it is sufficient to confer protection against therapeutic doses of many antibiotics. It has, therefore, been widely speculated that biocide misuse may have an insidious effect, contributing to the evolution and persistence of drug resistance within microbial communities. Whilst such notions are supported by laboratory studies that utilize pure cultures, recent evidence has strongly refuted such linkage within the general environment where complex, multispecies biofilms predominate and where biocidal products are routinely deployed. In such situations the competition, for nutrients and space, between community members of disparate sensitivities far outweighs any potential benefits bestowed by the changes in an individual's antimicrobial susceptibility.

Imaging sensor constellation for tomographic chemical cloud mapping.

PubMed

Cosofret, Bogdan R; Konno, Daisei; Faghfouri, Aram; Kindle, Harry S; Gittins, Christopher M; Finson, Michael L; Janov, Tracy E; Levreault, Mark J; Miyashiro, Rex K; Marinelli, William J

2009-04-01

A sensor constellation capable of determining the location and detailed concentration distribution of chemical warfare agent simulant clouds has been developed and demonstrated on government test ranges. The constellation is based on the use of standoff passive multispectral infrared imaging sensors to make column density measurements through the chemical cloud from two or more locations around its periphery. A computed tomography inversion method is employed to produce a 3D concentration profile of the cloud from the 2D line density measurements. We discuss the theoretical basis of the approach and present results of recent field experiments where controlled releases of chemical warfare agent simulants were simultaneously viewed by three chemical imaging sensors. Systematic investigations of the algorithm using synthetic data indicate that for complex functions, 3D reconstruction errors are less than 20% even in the case of a limited three-sensor measurement network. Field data results demonstrate the capability of the constellation to determine 3D concentration profiles that account for ~?86%? of the total known mass of material released.

Grounding language in action and perception: from cognitive agents to humanoid robots.

PubMed

Cangelosi, Angelo

2010-06-01

In this review we concentrate on a grounded approach to the modeling of cognition through the methodologies of cognitive agents and developmental robotics. This work will focus on the modeling of the evolutionary and developmental acquisition of linguistic capabilities based on the principles of symbol grounding. We review cognitive agent and developmental robotics models of the grounding of language to demonstrate their consistency with the empirical and theoretical evidence on language grounding and embodiment, and to reveal the benefits of such an approach in the design of linguistic capabilities in cognitive robotic agents. In particular, three different models will be discussed, where the complexity of the agent's sensorimotor and cognitive system gradually increases: from a multi-agent simulation of language evolution, to a simulated robotic agent model for symbol grounding transfer, to a model of language comprehension in the humanoid robot iCub. The review also discusses the benefits of the use of humanoid robotic platform, and specifically of the open source iCub platform, for the study of embodied cognition. Copyright 2010 Elsevier B.V. All rights reserved.

Exogenous contrast agents for thermoacoustic imaging: An investigation into the underlying sources of contrast

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

Ogunlade, Olumide, E-mail: o.ogunlade@ucl.ac.uk; Beard, Paul

2015-01-15

Purpose: Thermoacoustic imaging at microwave excitation frequencies is limited by the low differential contrast exhibited by high water content tissues. To overcome this, exogenous thermoacoustic contrast agents based on gadolinium compounds, iron oxide, and single wall carbon nanotubes have previously been suggested and investigated. However, these previous studies did not fully characterize the electric, magnetic, and thermodynamic properties of these agents thus precluding identification of the underlying sources of contrast. To address this, measurements of the complex permittivity, complex permeability, DC conductivity, and Grüneisen parameter have been made. These measurements allowed the origins of the contrast provided by each substancemore » to be identified. Methods: The electric and magnetic properties of the contrast agents were characterized at 3 GHz using two rectangular waveguide cavities. The DC conductivity was measured separately using a conductivity meter. Thermoacoustic signals were then acquired and compared to those generated in water. Finally, 3D electromagnetic simulations were used to decouple the different contributions to the absorbed power density. Results: It was found that the gadolinium compounds provided appreciable electric contrast but not originating from the gadolinium itself. The contrast was either due to dissociation of the gadolinium salt which increased ionic conductivity or its nondissociated polar fraction which increased dielectric polarization loss or a combination of both. In addition, very high concentrations were required to achieve appreciable contrast, to the extent that the Grüneisen parameter increased significantly and became a source of contrast. Iron oxide particles were found to produce low but measurable dielectric contrast due to dielectric polarization loss, but this is attributed to the coating of the particles not the iron oxide. Single wall carbon nanotubes did not provide measurable contrast of any type. Conclusions: It is concluded that gadolinium based contrast agents, iron oxide particles, and single walled carbon nanotubes have little intrinsic merit as thermoacoustic contrast agents. Simple electrolytes such as saline which yield high contrast based on ionic conductivity provide much higher dielectric contrast per unit solute concentration and are likely to be significantly more effective as contrast agents.« less

Monitoring the Stimulated Uncapping Process of Gold-Capped Mesoporous Silica Nanoparticles

DOE PAGES

Augspurger, Ashley E.; Sun, Xiaoxing; Trewyn, Brian G.; ...

2018-02-05

To establish a new method for tracking the interaction of nanoparticles with chemical cleaving agents, we exploited the optical effects caused by attaching 5-10 nm gold nanoparticles with molecular linkers to large mesoporous silica nanoparticles (MSN). At low levels of gold loading onto MSN, the optical spectra resemble colloidal suspensions of gold. As the gold is removed, by cleaving agents, the MSN revert to the optical spectra typical of bare silica. Time-lapse images of gold-capped MSN stationed in microchannels reveal that the rate of gold release is dependent on the concentration of the cleaving agent. Finally, the uncapping process wasmore » also monitored successfully for MSN endocytosed by A549 cancer cells, which produce the cleaving agent glutathione. These experiments demonstrate that the optical properties of MSN can be used to directly monitor cleaving kinetics, even in complex cellular settings.« less

Monitoring the Stimulated Uncapping Process of Gold-Capped Mesoporous Silica Nanoparticles.

PubMed

Augspurger, Ashley E; Sun, Xiaoxing; Trewyn, Brian G; Fang, Ning; Stender, Anthony S

2018-03-06

To establish a new method for tracking the interaction of nanoparticles with chemical cleaving agents, we exploited the optical effects caused by attaching 5-10 nm gold nanoparticles with molecular linkers to large mesoporous silica nanoparticles (MSN). At low levels of gold loading onto MSN, the optical spectra resemble colloidal suspensions of gold. As the gold is removed, by cleaving agents, the MSN revert to the optical spectra typical of bare silica. Time-lapse images of gold-capped MSN stationed in microchannels reveal that the rate of gold release is dependent on the concentration of the cleaving agent. The uncapping process was also monitored successfully for MSN endocytosed by A549 cancer cells, which produce the cleaving agent glutathione. These experiments demonstrate that the optical properties of MSN can be used to directly monitor cleaving kinetics, even in complex cellular settings.

Monitoring the Stimulated Uncapping Process of Gold-Capped Mesoporous Silica Nanoparticles

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

Augspurger, Ashley E.; Sun, Xiaoxing; Trewyn, Brian G.

To establish a new method for tracking the interaction of nanoparticles with chemical cleaving agents, we exploited the optical effects caused by attaching 5-10 nm gold nanoparticles with molecular linkers to large mesoporous silica nanoparticles (MSN). At low levels of gold loading onto MSN, the optical spectra resemble colloidal suspensions of gold. As the gold is removed, by cleaving agents, the MSN revert to the optical spectra typical of bare silica. Time-lapse images of gold-capped MSN stationed in microchannels reveal that the rate of gold release is dependent on the concentration of the cleaving agent. Finally, the uncapping process wasmore » also monitored successfully for MSN endocytosed by A549 cancer cells, which produce the cleaving agent glutathione. These experiments demonstrate that the optical properties of MSN can be used to directly monitor cleaving kinetics, even in complex cellular settings.« less

Using cyclodextrin complexation to enhance secondary photoprotection of topically applied ibuprofen.

PubMed

Godwin, Donald A; Wiley, Cody J; Felton, Linda A

2006-01-01

Each year millions of people are overexposed to the sun resulting in photodamage of the skin. Secondary photoprotection is the application of medicinal agents to the body after sun exposure to reduce this damage. The objective of this study was to determine the affects of hydroxypropyl-beta-cyclodextrin (HPCD) complexation on the secondary photoprotective properties of topically applied ibuprofen. Complexation of ibuprofen by HPCD was demonstrated by differential scanning calorimetry, while solubilities were determined using HPLC. A linear (r2>0.999) relationship was found between ibuprofen solubility and HPCD concentration. For subsequent experiments, the concentration of ibuprofen was held constant at the solubility in 10% HPCD (10.6 mg/ml), while the HPCD concentration varied from 0 to 20% (w/w). In vitro transdermal permeation experiments demonstrated a parabolic relationship between transdermal kinetic parameters and HPCD concentration, with maximum values for both flux and skin accumulation occurring with the 10% HPCD formulation. In vivo experiments were performed by exposing hairless mice to UV radiation and applying ibuprofen-HPCD formulations topically at various times following UV exposure. Edema and epidermal lipid damage data demonstrated that application of ibuprofen-HPCD formulations within 1h of UV exposure provided significant photoprotection.

Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand

NASA Astrophysics Data System (ADS)

Doherty, Rachel E.; Sazanovich, Igor V.; McKenzie, Luke K.; Stasheuski, Alexander S.; Coyle, Rachel; Baggaley, Elizabeth; Bottomley, Sarah; Weinstein, Julia A.; Bryant, Helen E.

2016-03-01

Photodynamic therapy that uses photosensitizers which only become toxic upon light-irradiation provides a strong alternative to conventional cancer treatment due to its ability to selectively target tumour material without affecting healthy tissue. Transition metal complexes are highly promising PDT agents due to intense visible light absorption, yet the majority are toxic even without light. This study introduces a small, photostable, charge-neutral platinum-based compound, Pt(II) 2,6-dipyrido-4-methyl-benzenechloride, complex 1, as a photosensitizer, which works under visible light. Activation of the new photosensitizer at low concentrations (0.1-1 μM) by comparatively low dose of 405 nm light (3.6 J cm-2) causes significant cell death of cervical, colorectal and bladder cancer cell lines, and, importantly, a cisplatin resistant cell line EJ-R. The photo-index of the complex is 8. We demonstrate that complex 1 induces irreversible DNA single strand breaks following irradiation, and that oxygen is essential for the photoinduced action. Neither light, nor compound alone led to cell death. The key advantages of the new drug include a remarkably fast accumulation time (diffusion-controlled, minutes), and photostability. This study demonstrates a highly promising new agent for photodynamic therapy, and attracts attention to photostable metal complexes as viable alternatives to conventional chemotherapeutics, such as cisplatin.

Photo-induced living radical polymerization of acrylates utilizing a discrete copper(II)-formate complex.

PubMed

Anastasaki, Athina; Nikolaou, Vasiliki; Brandford-Adams, Francesca; Nurumbetov, Gabit; Zhang, Qiang; Clarkson, Guy J; Fox, David J; Wilson, Paul; Kempe, Kristian; Haddleton, David M

2015-04-04

A photo-polymerization protocol, utilizing a pre-formed and well-characterized Cu(II) formate complex, [Cu(Me6-Tren)(O2CH)](ClO4), mediated by UV light is described. In the absence of additional reducing agents and/or photosensitizers, ppm concentrations of the oxidatively stable [Cu(Me6-Tren)(O2CH)](ClO4), furnish near-quantitative conversions within 2 h, yielding poly(acrylates) with low dispersities (∼1.10) and exceptional end-group fidelity, capable of undergoing in situ chain extension and block copolymerization.

[Fungal infectivities of implanted catheters due to Candida sp. Biofilms formation and resistance].

PubMed

Seddiki, S M L; Boucherit-Otmani, Z; Boucherit, K; Kunkel, D

2015-06-01

Candidemia are the most common fungal infections in hospitals. However, the catheters are subject to be altered by Candida biofilms which increase the risk of invasive nosocomial infections due to the high resistance to antifungal agents. Therefore, the minimum inhibitory concentrations of planktonic (MIC) and sessile cells (CIMS) were evaluated. To review the in vivo biofilms structures of Candida sp. formed on the inner and/or external surfaces of collected catheters, we used scanning electron microscopy (SEM). The level of biofilm resistance was assessed against two conventional antifungal agents: amphotericin B (AmB), which belongs to the class of polyenes, and fluconazole (FLZ) which is an azole. The SEM observation of biofilms of Candida sp. reveals complex structures. Compared to MICs, the calculation of CIMS showed an increase of 32 times with AmB and of 128 times with FLZ. Catheters offer an ideal surface to Candida sp. to form biofilms. This complex structure induces the increase of the resistance of sessile cells against two antifungal agents, AmB and FLZ. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Nuclear magnetic resonance study of Gd-based nanoparticles to tag boron compounds in boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Corti, M.; Bonora, M.; Borsa, F.; Bortolussi, S.; Protti, N.; Santoro, D.; Stella, S.; Altieri, S.; Zonta, C.; Clerici, A. M.; Cansolino, L.; Ferrari, C.; Dionigi, P.; Porta, A.; Zanoni, G.; Vidari, G.

2011-04-01

We report the investigation of new organic complexes containing a magnetic moment (Gd-based molecular nanomagnets), which can serve the double purpose of acting as boron neutron capture therapy (BNCT) agents, and at the same time act as contrast agents to detect the molecule in the tissue by a proton magnetic resonance imaging (MRI). We also explore the possibility of monitoring the concentration of the BNCT agent directly via proton and boron NMR relaxation. The absorption of 10B-enriched molecules inside tumoral liver tissues has been shown by NMR measurements and confirmed by α spectroscopy. A new molecular Gd-tagged nanomagnet and BNCT agent (GdBPA) has been synthesized and characterized measuring its relaxivity R1 between 10 kHz and 66 MHz, and its use as a contrast agent in MRI has been demonstrated. The NMR-based evidence of the absorption of GdBPA into living tumoral cells is also shown.

Mechanism of action of recombinant activated factor VII: an update.

PubMed

Hedner, Ulla

2006-01-01

Bleeding episodes in patients with hemophilia and inhibitors must be managed using agents that are hemostatically active in the absence of factor VIII or IX. Activated prothrombin complex concentrates have long been used in this context. However, the search for safer and more effective agents has led to the development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). This paper presents an update on the mechanism of action of rFVIIa, and describes how pharmacologic doses of this agent enhance thrombin production and thus contribute to the development of a stable, lysis-resistant fibrin plug at the site of vessel damage. This mechanism explains the reported efficacy of rFVIIa in a range of clinical situations characterized by impaired thrombin generation.

Speciation and isotope dilution analysis of gadolinium-based contrast agents in wastewater.

PubMed

Telgmann, Lena; Wehe, Christoph A; Birka, Marvin; Künnemeyer, Jens; Nowak, Sascha; Sperling, Michael; Karst, Uwe

2012-11-06

The fate of Gadolinium (Gd)-based contrast agents for magnetic resonance imaging (MRI) during sewage treatment was investigated. The total concentration of Gd in influent and effluent 2 and 24 h composite samples was determined by means of isotope dilution analysis. The balancing of Gd input and output of a sewage plant over seven days indicated that approximately 10% of the Gd is removed during treatment. Batch experiments simulating the aeration tank of a sewage treatment plant confirmed the Gd complex removal during activated sludge treatment. For speciation analysis of the Gd complexes in wastewater samples, high performance liquid chromatography (HPLC) was hyphenated to inductively coupled plasma sector field mass spectrometry (ICP-SFMS). Separation of the five predominantly used contrast agents was carried out on a new hydrophilic interaction liquid chromatography stationary phase in less than 15 min. A limit of detection (LOD) of 0.13 μg/L and a limit of quantification of 0.43 μg/L could be achieved for the Gd chelates without having to apply enrichment techniques. Speciation analysis of the 24 h composite samples revealed that 80% of the Gd complexes are present as Gd-BT-DO3A in the sampled treatment plant. The day-of-week dependent variation of the complex load followed the variation of the total Gd load, indicating a similar behavior. The analysis of sewage sludge did not prove the presence of anthropogenic Gd. However, in the effluent of the chamber filter press, which was used for sludge dewatering, two of the contrast agents and three other unknown Gd species were observed. This indicates that species transformation took place during anaerobic sludge treatment.

Branched-chain amino acids complex inhibits melanogenesis in B16F0 melanoma cells.

PubMed

Cha, Jae-Young; Yang, Hyun-Ju; Moon, Hyung-In; Cho, Young-Su

2012-04-01

Present study was investigated the effect of each or complex of three branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) on melanin production in B16F0 melanoma cells treated with various concentrations (1-16 mM) for 72 h. Among the 20 amino acids, lysine and glycine showed the highest activities of DPPH radical scavenging and mushroom tyrosinase inhibition, respectively. Each and combination of BCAAs reduced melanogenesis in a concentration-dependent manner without any morphological changes and cell viability in melanoma cells. Present study was also investigated the inhibitory effects of each or complex of BCAAs at each 10 mM concentration on the 100 μM IBMX-mediated stimulation of melanogenesis in melanoma cells for 72 h and found that IBMX treatment was stimulated to enhance melanin synthesis and that the complex of BCAAs was the most effectively inhibited in the melanin amounts of cellular and extracellular and the whitening the cell pellet. When the inhibitory effect of BCAAs on tyrosinase was examined by intracellular tyrosinase assay, both isoleucine and valine exhibit slightly inhibition, but leucine and combination of BCAAs did not inhibit the cell-derived tyrosinase activity. Present study demonstrated that complex of BCAAs inhibited melanin production without changes intercellular tyrosinase activity. Thus, the complex of BCAAs may be used in development of safe potentially depigmenting agents.

THE SOLVENT EXTRACTION OF NITROSYLRUTHENIUM BY TRILAURYLAMINE IN NITRATE SYSTEM. Summary Report for the Period, July 1, 1960 to March 31, 1962

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

Skavdahl, R.E.; Mason, E.A.

1962-06-01

An investigation of the solvent extraction characteristics of the nitro and nitrato complexes of nitrosylruthenium in nitric acid- sodium nitrate aqueous media was conducted. As the organic extractant phase, a solution of trilaurylamine (TLA) in toluene was utilized. In addition to the usual process parameter variation tyne of experiment, a rapid dilution type of experiment was used extensively to determine qualitative and semiquantitative results regarding the degree of extractability and concentration of the more extractable species of the nitrato complexes of nitrosylruthenium. It was found that the acids of the tetra-nitrato and pentanitrato complexes were the more extractable species formore » that set of complexes and that the acid of the penta-nitrato complex was the more extractable of the two. It was observed that for freshly prepared solutions, the dinitro complex of nitrosylruthenium was much more extractable than the gross nitrato complexes solutions. Nitro complexes in general, and the dinitro complex in particular, may be the controlling agent in ruthenium decontamination of spent nuclear fuel processed by solvent extraction methods. The experimental results from both sets of complexes could be more meaningfully correlated on the basis of unbound nitric acid concentration in the organic phase than on the basis of nitric acid concentration in the aqueous phase. The extraction of nitric acid by TLA from nitric acid-sodium nitrate aqueous solutions was investigated and the results correlated on the basis of activity of the undissociated nitric acid in the aqueous phase. (auth)« less

Application of 1H and 23Na magic angle spinning NMR spectroscopy to define the HRBC up-taking of MRI contrast agents

NASA Astrophysics Data System (ADS)

Calabi, Luisella; Paleari, Lino; Biondi, Luca; Linati, Laura; De Miranda, Mario; Ghelli, Stefano

2003-09-01

The up-take of Gd(III) complexes of BOPTA, DTPA, DOTA, EDTP, HPDO3A, and DOTP in HRBC has been evaluated by measuring the lanthanide induced shift (LIS) produced by the corresponding dysprosium complexes (DC) on the MAS-NMR resonances of water protons and free sodium ions. These complexes are important in their use as MRI contrast agents (MRI-CA) in diagnostics. 1H and 23Na MAS-NMR spectra of HRBC suspension, collected at 9.395 T, show only one signal due to extra- and intra-cellular water (or sodium). In MAS spectra, the presence of DC in a cellular compartment produces the LIS of only the nuclei (water proton or sodium) in that cellular compartment and this LIS can be related to the DC concentrations (by the experimental curves of LIS vs. DC concentrations) collected in the physiological solution. To obtain correct results about LIS, the use of MAS technique is mandatory, because it guarantees the only the nuclei staying in the same cellular compartment where the LC is present show the LIS. In all the cases considered, the addition of the DC to HRBC (100% hematocrit) produced a shift of only the extra-cellular water (or sodium) signal and the gradient of concentration ( GC) between extra- and intra-cellular compartments resulted greater than 100:1, when calculated by means of sodium signals. These high values of GC are direct proofs that none of the tested dysprosium complexes crosses the HRBC membrane. Since the DC are iso-structural to the gadolinium complexes the corresponding gadolinium ones (MRI-CA) do not cross the HRBC membrane and, consequently, they are not up-taken in HRBC. The GC values calculated by means of water proton signals resulted much lower than those obtained by sodium signals. This proves that the choice of the isotope is a crucial step in order to use this method in the best way. In fact, GC value depends on the lowest detectable LIS which, in turn, depends on the nature of the LC (lanthanide complex) and the observed isotopes.

Targeting HSP70-induced thermotolerance for design of thermal sensitizers.

PubMed

Calderwood, S K; Asea, A

2002-01-01

Thermal therapy has been shown to be an extremely powerful anti-cancer agent and a potent radiation sensitizer. However, the full potential of thermal therapy is hindered by a number of considerations including highly conserved heat resistance pathways in tumour cells and inhomogeneous heating of deep-seated tumours due to energy deposition and perfusion issues. This report reviews recent progress in the development of hyperthermia sensitizing drugs designed to specifically amplify the effects of hyperthermia. Such agents might be particularly useful in situations where heating is not adequate for the full biological effect or is not homogeneously delivered to tumours. The particular pathway concentrated on is thermotolerance, a complex, inducible cellular response that leads to heat resistance. This paper will concentrate on the molecular pathways of thermotolerance induction for designing inhibitors of heat resistance/thermal sensitizers, which may allow the full potential of thermal therapy to be utilized.

Bionano Interaction Study on Antimicrobial Star-Shaped Peptide Polymer Nanoparticles.

PubMed

Lam, Shu J; Wong, Edgar H H; O'Brien-Simpson, Neil M; Pantarat, Namfon; Blencowe, Anton; Reynolds, Eric C; Qiao, Greg G

2016-12-14

'Structurally nanoengineered antimicrobial peptide polymers' (SNAPPs), in the form of star-shaped peptide polymer nanoparticles, have been recently demonstrated as a new class of antimicrobial agents with superior in vitro and in vivo efficacy against Gram-negative pathogens, including multidrug-resistant species. Herein, we present a detailed bionano interaction study on SNAPPs by assessing their antimicrobial activities against several Gram-negative bacteria in complex biological matrices. Simulated body fluid and animal serum were used as test media to reveal factors that influence the antimicrobial efficacy of SNAPPs. With the exception of Acinetobacter baumannii, the presence of divalent cations at physiological concentrations reduced the antimicrobial efficacy of SNAPPs from minimum inhibitory concentrations (MICs) within the nanomolar range (40-300 nM) against Escherichia coli, Pseudomanas aeruginosa, and Klebsiella pneumoniae to 0.6-4.7 μM. By using E. coli as a representative bacterial species, we demonstrated that the reduction in activity was due to a decrease in the ability of SNAPPs to cause outer and inner membrane disruption. This effect could be reversed through coadministration with a chelating agent. Interestingly, the potency of SNAPPs against A. baumannii was retained even under high salt concentrations. The presence of serum proteins was also found to affect the interaction of SNAPPs with bacterial membranes, possibly through intermolecular binding. Collectively, this study highlights the need to consider the possible interactions of (bio)molecules present in vivo with any new antimicrobial agent under development. We also demonstrate that outer membrane disruption/destabilization is an important but hitherto under-recognized target for the antimicrobial action of peptide-based agents, such as antimicrobial peptides (AMPs). Overall, the findings presented herein could aid in the design of more efficient peptide-based antimicrobial agents with uncompromised potency even under physiological conditions.

Low-level (PPB) determination of cisplatin in cleaning validation (rinse water) samples. II. A high-performance liquid chromatographic method.

PubMed

Raghavan, R; Burchett, M; Loffredo, D; Mulligan, J A

2000-04-01

A high-performance liquid chromatographic (HPLC) method is described for the determination of residual levels of cisplatin from extracts of surfaces with very low surface area; from extracts of surfaces of coupons made of Teflon (polytetrafluoroethylene, PTFE), stainless steel, and glass; and in aqueous solution collected after rinsing equipment and parts. Initially, the method was developed to determine cisplatin at concentrations ranging from 20 to 200 ng/ml by direct injection. Retaining the same method conditions, the scope of the method was expanded by the addition of a sample preconcentration step, allowing analyses at levels ranging from 0.5 ng to 20 ng/ml. Preconcentration is necessary for the determination of cisplatin in rinse waters at a quantifiable concentration of about 2 PPB. Under these conditions, the detection limit is about 0.2 to 0.3 ng/ml. Residual cisplatin on different types of surfaces, including surfaces with very low surface area, can be determined by swabbing each test surface with a derivatizing solution. The cisplatin recovered in the swabbing solution can be analyzed by HPLC using direct injection or preconcentration, depending on the expected level of cisplatin in the sample. Initial methods were developed to quantitate at a cisplatin concentration of about 100 PPB or higher in solution extracted from surfaces. However, when surface areas are limited because of the size of the parts, solution concentration becomes very low as a result of the minimum volume required for extraction. To support the application of swabbing techniques to surface analysis, stainless steel, Teflon, and glass surfaces were spiked with cisplatin at 2.5 to 20 ng/cm2. Satisfactory overall recoveries of 90% +/- 10% were obtained from all surfaces. Cisplatin has no ultraviolet/visible (UV/Vis) spectral-active functional group that can be used to detect low levels of cisplatin. Hence, diethyldithiocarbamate (DDTC) was used as a derivatizing agent to increase sensitivity to UV absorption at 340 nm. Diethyldithiocarbamate forms complexes with the platinum in cisplatin to yield a platinum-DDTC (Pt-DDTC) complex with a high molar-extinction coefficient. The Pt(DDTC)2 complex thus formed was chromatographically separated and the quantitated by comparison of its detector response to that of a similarly derivatized standard preparation. DDTC also has application as a cleaning agent for cisplatin (e.g., for production equipment cleaning, spill cleanup). Destruction of cisplatin can be affected by the reaction of cisplatin with this cleaning agent. Derivatization of cisplatin will convert active cisplatin to platinum-DDTC on surfaces or in solution. Final cleaning can be accomplished using a water-for-injection rinse. After such a cleaning process, the rinse water, when collected and analyzed, showed levels of free cisplatin less than the detection concentration of 0.2 PPB and a total platinum concentration less than 10 PPB as Pt-DDTC complex.

Neurosteroids in hepatic encephalopathy: Novel insights and new therapeutic opportunities.

PubMed

Butterworth, Roger F

2016-06-01

Hepatic encephalopathy (HE) is a serious neuropsychiatric disorder resulting from liver failure. Symptoms of HE include mild cognitive impairment, stupor and coma. Morphological changes to neuroglia (both astrocytes and microglia) occur in HE consisting of cytotoxic brain edema (astrocyte swelling) in acute liver failure and Alzheimer type-2 astrocytosis in cirrhosis. Visual-evoked responses in animals with liver failure and HE manifest striking similarities to those in animals treated with agonists of the GABA-A receptor complex. Neurosteroids are synthesized in brain following activation of translocator protein (TSPO), a mitochondrial neuroglial cholesterol-transporter protein. TSPO sites are activated in both animal models of HE as well as in autopsied brain tissue from HE patients. Activation of TSPO sites results in increased cholesterol transport into the mitochondrion followed by stimulation of a metabolic pathway culminating in the synthesis of allopregnanolone (ALLO) and tetrahydrodeoxycorticosterone (THDOC), neurosteroids with potent positive allosteric modulatory action on the GABA-A receptor complex. Concentrations of ALLO and THDOC in brain tissue from mice with HE resulting from toxic liver injury are sufficient to induce sedation in animals of the same species and significant increases in concentrations of ALLO have been reported in autopsied brain tissue from cirrhotic patients with HE leading to the proposal that "increased GABAergic tone" in HE results from that increased brain concentrations of this neurosteroid. Agents with the potential to decrease neurosteroid synthesis and/or prevent their modulatory actions on the GABA-A receptor complex may provide novel approaches to the management and treatment of HE. Such agents include indomethacin, benzodiazepine receptor inverse agonists and a novel series of compounds known as GABA-A receptor-modulating steroid antagonists (GAMSA). Copyright © 2015 Elsevier Ltd. All rights reserved.

Reclamation with Recovery of Radionuclides and Toxic Metals from Contaminated Materials, Soils, and Wastes

NASA Technical Reports Server (NTRS)

Francis, A. J.; Dodge, C. J.

1993-01-01

A process has been developed at Brookhaven National Laboratory (BNL) for the removal of metals and radionuclides from contaminated materials, soils, and waste sites. In this process, citric acid, a naturally occurring organic complexing agent, is used to extract metals such as Ba, Cd, Cr, Ni, Zn, and radionuclides Co, Sr, Th, and U from solid wastes by formation of water soluble, metal-citrate complexes. Citric acid forms different types of complexes with the transition metals and actinides, and may involve formation of a bidentate, tridentate, binuclear, or polynuclear complex species. The extract containing radionuclide/metal complex is then subjected to microbiological degradation followed by photochemical degradation under aerobic conditions. Several metal citrate complexes are biodegraded, and the metals are recovered in a concentrated form with the bacterial biomass. Uranium forms binuclear complex with citric acid and is not biodegraded. The supernatant containing uranium citrate complex is separated and upon exposure to light, undergoes rapid degradation resulting in the formation of an insoluble, stable polymeric form of uranium. Uranium is recovered as a precipitate (polyuranate) in a concentrated form for recycling or for appropriate disposal. This treatment process, unlike others which use caustic reagents, does not create additional hazardous wastes for disposal and causes little damage to soil which can then be returned to normal use.

Pushing the sensitivity envelope of lanthanide-based magnetic resonance imaging (MRI) contrast agents for molecular imaging applications.

PubMed

Aime, Silvio; Castelli, Daniela Delli; Crich, Simonetta Geninatti; Gianolio, Eliana; Terreno, Enzo

2009-07-21

Contrast in magnetic resonance imaging (MRI) arises from changes in the intensity of the proton signal of water between voxels (essentially, the 3D counterpart of pixels). Differences in intervoxel intensity can be significantly enhanced with chemicals that alter the nuclear magnetic resonance (NMR) intensity of the imaged spins; this alteration can occur by various mechanisms. Paramagnetic lanthanide(III) complexes are used in two major classes of MRI contrast agent: the well-established class of Gd-based agents and the emerging class of chemical exchange saturation transfer (CEST) agents. A Gd-based complex increases water signal by enhancing the longitudinal relaxation rate of water protons, whereas CEST agents decrease water signal as a consequence of the transfer of saturated magnetization from the exchangeable protons of the agent. In this Account, we survey recent progress in both areas, focusing on how MRI is becoming a more competitive choice among the various molecular imaging methods. Compared with other imaging modalities, MRI is set apart by its superb anatomical resolution; however, its success in molecular imaging suffers because of its intrinsic insensitivity. A relatively high concentration of molecular agents (0.01-0.1 mM) is necessary to produce a local alteration in the water signal intensity. Unfortunately, the most desirable molecules for visualization in molecular imaging are present at much lower concentrations, in the nano- or picomolar range. Therefore, augmenting the sensitivity of MRI agents is key to the development of MR-based molecular imaging applications. In principle, this task can be tackled either by increasing the sensitivity of the reporting units, through the optimization of their structural and dynamic properties, or by setting up proper amplification strategies that allow the accumulation of a huge number of imaging reporters at the site of interest. For Gd-based agents, high sensitivities can be attained by exploiting a range of nanosized carriers (micelles, liposomes, microemulsions, and the like, as well as biological structures such as apoferritin and lipoproteins) properly loaded with Gd-based chelates. Furthermore, the sensitivity of Gd-based agents can be markedly affected either by their interactions with biological structures or by their cellular localization. For CEST agents, a huge sensitivity enhancement has been obtained by using the water molecules contained in the inner cavity of liposomes as the exchangeable source of protons for magnetization transfer. Several "tricks" (for example, the use of multimeric lanthanide(III) shift reagents, changes in the shape of the liposome container, and so forth) have been devised to improve the chemical shift separation between the intraliposomal water and the "bulk" water resonances. Overall, excellent sensitivity enhancements have been obtained for both classes of agents, enabling their use in MR molecular imaging applications.

Approach for Autonomous Control of Unmanned Aerial Vehicle Using Intelligent Agents for Knowledge Creation

NASA Technical Reports Server (NTRS)

Dufrene, Warren R., Jr.

2004-01-01

This paper describes the development of a planned approach for Autonomous operation of an Unmanned Aerial Vehicle (UAV). A Hybrid approach will seek to provide Knowledge Generation through the application of Artificial Intelligence (AI) and Intelligent Agents (IA) for UAV control. The applications of several different types of AI techniques for flight are explored during this research effort. The research concentration is directed to the application of different AI methods within the UAV arena. By evaluating AI and biological system approaches. which include Expert Systems, Neural Networks. Intelligent Agents, Fuzzy Logic, and Complex Adaptive Systems, a new insight may be gained into the benefits of AI and CAS techniques applied to achieving true autonomous operation of these systems. Although flight systems were explored, the benefits should apply to many Unmanned Vehicles such as: Rovers. Ocean Explorers, Robots, and autonomous operation systems. A portion of the flight system is broken down into control agents that represent the intelligent agent approach used in AI. After the completion of a successful approach, a framework for applying an intelligent agent is presented. The initial results from simulation of a security agent for communication are presented.

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

McAfee, J.G.; Krauss, D.J.; Subramanian, G.

The 3-hour biodistribution of /sup 99m/Tc complexes of five diphosphonates (HMDP, NMMDP, DMAD, DPD, and APD), imidodiphosphonate (IDP), and pyrophosphate (PYP) was compared in rats with segmental renal infarction induced by a 1-hour occlusion of a renal artery branch. /sup 95m/Tc labeled MDP was a reference substance in all animals. Three agents (APD, HMDP and IDP) had a higher infarct/normal kidney concentration ratio than MDP, the latter two by virtue of a lower content in normal kidney. HMDP, DPD, and IDP had very high liver concentrations. DPD showed relatively high concentrations in soft tissues and blood. The blood and kidneymore » levels of PYP were higher than those of MDP but the infarct/normal kidney ratios were similar. None of the agents had a higher uptake in bone than MDP: four had a significantly lower uptake. The increased concentration of /sup 99m/Tc MDP in the infarcts was readily seen in camera images one day after renal artery occlusion, but not at three or seven days. Increased diphosphonate uptake was accompanied by an influx of calcium in both cortex and medulla. The accumulation of diphosphonate in areas of infarction was not modified by infusions of verapamil or Captopril.« less

Microcosm assays and Taguchi experimental design for treatment of oil sludge containing high concentration of hydrocarbons.

PubMed

Castorena-Cortés, G; Roldán-Carrillo, T; Zapata-Peñasco, I; Reyes-Avila, J; Quej-Aké, L; Marín-Cruz, J; Olguín-Lora, P

2009-12-01

Microcosm assays and Taguchi experimental design was used to assess the biodegradation of an oil sludge produced by a gas processing unit. The study showed that the biodegradation of the sludge sample is feasible despite the high level of pollutants and complexity involved in the sludge. The physicochemical and microbiological characterization of the sludge revealed a high concentration of hydrocarbons (334,766+/-7001 mg kg(-1) dry matter, d.m.) containing a variety of compounds between 6 and 73 carbon atoms in their structure, whereas the concentration of Fe was 60,000 mg kg(-1) d.m. and 26,800 mg kg(-1) d.m. of sulfide. A Taguchi L(9) experimental design comprising 4 variables and 3 levels moisture, nitrogen source, surfactant concentration and oxidant agent was performed, proving that moisture and nitrogen source are the major variables that affect CO(2) production and total petroleum hydrocarbons (TPH) degradation. The best experimental treatment yielded a TPH removal of 56,092 mg kg(-1) d.m. The treatment was carried out under the following conditions: 70% moisture, no oxidant agent, 0.5% of surfactant and NH(4)Cl as nitrogen source.

Investigation into 64Cu-labeled Bis(selenosemicarbazone) and Bis(thiosemicarbazone) complexes as hypoxia imaging agents.

PubMed

McQuade, Paul; Martin, Katherine E; Castle, Thomas C; Went, Michael J; Blower, Philip J; Welch, Michael J; Lewis, Jason S

2005-02-01

Cu-diacetyl-bis(N4-methylthiosemicarbazone) [Cu-ATSM], although excellent for oncology applications, may not be suitable for delineating cardiovascular or neurological hypoxia. For this reason, new Cu hypoxia positron emission tomography (PET) imaging agents are being examined to search for a higher selectivity for hypoxic or ischemic tissue at higher oxygen concentrations found in these tissues. Two approaches are to increase alkylation or to replace the sulfur atoms with selenium, resulting in the formation of selenosemicarbazones. Three 64Cu-labeled selenosemicarbazone complexes were synthesized and one was screened for hypoxia selectivity in vitro using EMT-6 mouse mammary carcinoma cells. Rodent biodistribution and small animal PET images were obtained from BALB/c mice implanted with EMT-6 tumors. One alkylated thiosemicarbazone was synthesized and examined. Of the three bis(selenosemicarbazone) ligands synthesized and examined, only 64Cu-diacetyl-bis(selenosemicarbazone) [64Cu-ASSM] was isolated in high-enough radiochemical purity to undertake cell uptake experiments where uptake was shown to be independent of oxygen concentration. The bis(thiosemicarbazone) complex synthesized, 64Cu-diacetyl-bis(N4-ethylthiosemicarbazone) [64Cu-ATSE], showed hypoxia selectivity similar to 64Cu-ATSM although at a higher oxygen concentration. Biodistribution studies for 64Cu-ASSM and 64Cu-ATSE showed high tumor uptake at 20 min (64Cu-ASSM, 10.33+/-0.78% ID/g; 64Cu-ATSE, 7.71+/-0.46% ID/g). PET images of EMT-6 tumor-bearing mice visualized the tumor with 64Cu-ATSE and revealed hypoxia selectivity consistent with the in vitro data. Of the compounds synthesized, only 64Cu-ASSM and 64Cu-ATSE could be examined in vitro and in vivo. Although the stability of bis(selenosemicarbazone) complexes increased upon addition of methyl groups to the diimine backbone, the fully alkylated species, 64Cu-ASSM, demonstrated no hypoxia selectivity. However, the additional alkylation present in Cu-ATSE modifies the hypoxia selectivity and in vivo properties when compared with Cu-ATSM.

Core-shell magnetite-silica composite nanoparticles enhancing DNA damage induced by a photoactive platinum-diimine complex in red light.

PubMed

Zhang, Zhigang; Chai, Aiyun

2012-12-01

Lack of solubility under physiological conditions poses an additional risk for toxicity and side effects for intravenous delivery of the photodynamic therapeutic agent in vivo. Employing magnetite-silica composite nanoparticles as carriers of the photodynamic therapeutic agents may be a promising way to solve the problem. In this study, core-shell magnetite-silica composite nanoparticles were prepared by a sol-gel method, and characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy and dynamic light scattering, then they were used as carriers of a photoactive platinum diimine complex. The interactions of the photosensitizer-loaded magnetic composite nanoparticles with DNA in red light were monitored by agarose-gel electrophoresis. The results suggest that high doses of magnetite-silica composite nanoparticles might facilitate the transformation of covalently closed circular (ccc)-DNA band to open circular (oc)-DNA band though they are harmless to DNA at their low concentrations, therefore enhancing the extent of DNA damage caused by the metal complex in red light. Copyright © 2012 Elsevier Inc. All rights reserved.

Preparation, quality control and biodistribution assessment of ¹⁵³Sm-BPAMD as a novel agent for bone pain palliation therapy.

PubMed

Rabie, Ali; Enayati, Razieh; Yousefnia, Hassan; Jalilian, Amir Reza; Shamsaei, Mojtaba; Zolghadri, Samaneh; Bahrami-Samani, Ali; Hosntalab, Mohammad

2015-12-01

Various phosphonate ligands labeled with β(-)-emitting radionuclides have shown good efficacy for bone pain palliation. In this study, a new agent for bone pain palliation has been developed. ¹⁵³Sm-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (¹⁵³Sm-BPAMD) complex was prepared using BPAMD ligand and ¹⁵³SmCl3. The effect of various parameters on the labeling yield of ¹⁵³Sm-BPAMD including ligand concentration, pH, temperature and reaction time were studied. Radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography (ITLC). Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. Partition coefficient and hydroxyapatite (HA) binding of the complex were investigated and biodistribution studies (SPECT imaging and scarification) were performed after injection of the complex to Syrian mice up to 48 h post-injection. The biodistribution of the complex was compared with the biodistribution of the ¹⁵³Sm cation in the same type mice. ¹⁵³Sm-BPAMD was prepared in high radiochemical purity >98% and specific activity of 267 GBq/mmol at the optimal conditions. The complex demonstrated significant stability at room temperature and in human serum at least for 48 h. HA binding assay demonstrated that at the amount of more than 5 mg, approximately, all radiolabeled complex was bound to HA. At the pH 7.4, LogP o/w was -1.86 ± 0.02. Both SPECT and scarification showed major accumulation of the labeled compound in the bone tissue. The results show that ¹⁵³Sm-BPAMD has interesting characteristics as an agent for bone pain palliation; however, further biological studies in other mammals are still needed.

A prospective evaluation of contrast and radiation dose and image quality in cardiac CT in children with complex congenital heart disease using low-concentration iodinated contrast agent and low tube voltage and current.

PubMed

Hou, Qiao-Ru; Gao, Wei; Sun, Ai-Min; Wang, Qian; Qiu, Hai-Sheng; Wang, Fang; Hu, Li-Wei; Li, Jian-Ying; Zhong, Yu-Min

2017-02-01

To the assess image quality, contrast dose and radiation dose in cardiac CT in children with congenital heart disease (CHD) using low-concentration iodinated contrast agent and low tube voltage and current in comparison with standard dose protocol. 110 patients with CHD were randomized to 1 of the 2 scan protocols: Group A (n = 45) with 120 mA tube current and contrast agent of 270 mgI/ml in concentration (Visipaque ™ ; GE Healthcare Ireland, Co., Cork, UK); and Group B (n = 65) with the conventional 160 mA and 370 mgI/ml concentration contrast (Iopamiro ® ; Shanghai Bracco Sine Pharmaceutical Corp Ltd, Shanghai, China). Both groups used 80 kVp tube voltage and were reconstructed with 70% adaptive statistical iterative reconstruction algorithm. The CT value and noise in aortic arch were measured and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. A five-point scale was used to subjectively evaluate image quality. Contrast and radiation dose were recorded. There was no difference in age and weight between the two groups (all p > 0.05). The iodine load and radiation dose in Group A were statistically lower (3976 ± 747 mgI vs 5763 ± 1018 mgI in iodine load and 0.60 ± 0.08 mSv vs 0.77 ± 0.10 mSv in effective dose; p < 0.001). However, image noise, CT value, CNR, SNR and subjective image quality for the two groups were similar (all p > 0.05), and with good agreement between the two observers. Comparing the surgery results, the diagnostic accuracy for extracardiac and intracardiac defects for Group A was 96% and 92%, respectively, while the corresponding numbers for Group B were 95% and 93%. Compared with the standard dose protocol, the use of low tube voltage (80 kVp), low tube current (120 mA) and low-concentration iodinated contrast agent (270 mgI/ml) enables a reduction of 30% in iodine load and 22% in radiation dose while maintaining compatible image quality and diagnostic accuracy. Advances in knowledge: The new cardiac CT scanning protocol can largely reduce the adverse effects of radiation and contrast media to children. Meanwhile, it also can be used effectively to examine complex CHD.

The Urinary Antibiotic 5-Nitro-8-Hydroxyquinoline (Nitroxoline) Reduces the Formation and Induces the Dispersal of Pseudomonas aeruginosa Biofilms by Chelation of Iron and Zinc

PubMed Central

Klinger, M.; Hermann, B.; Sachse, S.; Nietzsche, S.; Makarewicz, O.; Keller, P. M.; Pfister, W.; Straube, E.

2012-01-01

Since cations have been reported as essential regulators of biofilm, we investigated the potential of the broad-spectrum antimicrobial and cation-chelator nitroxoline as an antibiofilm agent. Biofilm mass synthesis was reduced by up to 80% at sub-MIC nitroxoline concentrations in Pseudomonas aeruginosa, and structures formed were reticulate rather than compact. In preformed biofilms, viable cell counts were reduced by 4 logs at therapeutic concentrations. Complexation of iron and zinc was demonstrated to underlie nitroxoline's potent antibiofilm activity. PMID:22926564

A Re-evaluation of the Ferrozine Method for Dissolved Iron: The Effect of Organic Interferences

NASA Astrophysics Data System (ADS)

Balind, K.; Barber, A.; Gelinas, Y.

2016-12-01

Among the most commonly used analytical methods in geochemistry is the ferrozine method for determining dissolved iron concentration in water (1). This cheap and easy-to-use spectrophotometric method involves a complexing agent (ferrozine), a reducing agent (hydroxylamine-HCl) and buffer (ammonium acetate with ammonium hydroxide). Previous studies have demonstrated that complex organic matter (OM) originating from the Suwannee River did not lead to a significantly underestimation of the measured iron content in OM amended iron solutions (2). The authors concluded that this method could be used even in organic rich (i.e., 25 mg/L) waters. Here we compare the concentration of Fe measured using this spectrophotometric method to the total Fe as measured by ICP-MS in the presence/absence of specific organic molecules to ascertain if they interfere with the ferrozine method. We show that certain molecules with hydroxyl and carboxyl functional groups as well as multi-dentate chelating species have a significant effect on the measured iron concentrations. Two possible mechanisms likely are responsible for the inefficiency of this method in the presence of specific organic molecules; 1) incomplete reduction of Fe(III) bound to organic molecules, or 2) competition between the OM and ferrozine for the available iron. We address these possibilities separately by varying the experimental conditions. These methodological artifacts may have far reaching implications due to the extensive use of this method. Stookey, L. L., Anal. Chem., 42, 779 (1970). Viollier, E., et al., Applied Geochem., 15, 785 (2000).

Quantitative chemical exchange saturation transfer (qCEST) MRI - omega plot analysis of RF-spillover-corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate.

PubMed

Wu, Renhua; Xiao, Gang; Zhou, Iris Yuwen; Ran, Chongzhao; Sun, Phillip Zhe

2015-03-01

Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST-weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH-dependent exchange rate followed a dominantly base-catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system. Copyright © 2015 John Wiley & Sons, Ltd.

Mu Opioids and Their Receptors: Evolution of a Concept

PubMed Central

Pan, Ying-Xian

2013-01-01

Opiates are among the oldest medications available to manage a number of medical problems. Although pain is the current focus, early use initially focused upon the treatment of dysentery. Opium contains high concentrations of both morphine and codeine, along with thebaine, which is used in the synthesis of a number of semisynthetic opioid analgesics. Thus, it is not surprising that new agents were initially based upon the morphine scaffold. The concept of multiple opioid receptors was first suggested almost 50 years ago (Martin, 1967), opening the possibility of new classes of drugs, but the morphine-like agents have remained the mainstay in the medical management of pain. Termed mu, our understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years. Early pharmacological studies identified three major classes of receptors, helped by the discovery of endogenous opioid peptides and receptor subtypes—primarily through the synthesis of novel agents. These chemical biologic approaches were then eclipsed by the molecular biology revolution, which now reveals a complexity of the morphine-like agents and their receptors that had not been previously appreciated. PMID:24076545

Screening of chelating ligands to enhance mercury accumulation from historically mercury-contaminated soils for phytoextraction.

PubMed

Wang, Jianxu; Xia, Jicheng; Feng, Xinbin

2017-01-15

Screening of optimal chelating ligands which not only have high capacities to enhance plant uptake of mercury (Hg) from soil but also can decrease bioavailable Hg concentration in soil is necessary to establish a viable chemically-assisted phytoextraction. Therefore, Brassica juncea was exposed to historically Hg-contaminated soil (total Hg, 90 mg kg -1 ) to investigate the efficiency of seven chelating agents [ammonium thiosulphate, sodium thiosulphate, ammonium sulfate, ammonium chloride, sodium nitrate, ethylenediaminetetraacetic acid (EDTA), and sodium sulfite] at enhancing Hg phytoextraction; the leaching of bioavailable Hg caused by these chelating agents was also investigated. The Hg concentration in control (treated with double-distilled water) plant tissues was below 1 mg kg -1 . The remarkably higher Hg concentration was found in plants receiving ammonium thiosulphate and sodium sulfite treatments. The bioaccumulation factors and translocation factors of ammonium thiosulphate and sodium sulfite treatments were significantly higher than those of the other treatments. The more efficient uptake of Hg by plants upon treatment with ammonium thiosulphate and sodium sulfite compared to the other treatments might be explained by the formation of special Hg-thiosulphate complexes that could be preferentially taken up by the roots and transported in plant tissues. The application of sulfite significantly increased bioavailable Hg concentration in soil compared with that in initial soil and control soil, whereas ammonium thiosulphate significantly decreased bioavailable Hg concentration. The apparent decrease of bioavailable Hg in ammonium thiosulphate-treated soil compared with that in sodium sulfite-treated soil might be attributable to the unstable Hg-thiosulphate complexes formed between thiosulphate and Hg; they could react to produce less bioavailable Hg in the soil. The results of this study indicate that ammonium thiosulphate may be an optimal chelating ligand for phytoextraction due to its great potential to enhance Hg accumulation in plants while decreasing bioavailable Hg concentration in the soil. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multi-agent simulation of generation expansion in electricity markets.

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

Botterud, A; Mahalik, M. R.; Veselka, T. D.

2007-06-01

We present a new multi-agent model of generation expansion in electricity markets. The model simulates generation investment decisions of decentralized generating companies (GenCos) interacting in a complex, multidimensional environment. A probabilistic dispatch algorithm calculates prices and profits for new candidate units in different future states of the system. Uncertainties in future load, hydropower conditions, and competitors actions are represented in a scenario tree, and decision analysis is used to identify the optimal expansion decision for each individual GenCo. We test the model using real data for the Korea power system under different assumptions about market design, market concentration, and GenCo'smore » assumed expectations about their competitors investment decisions.« less

The kinetics of lanthanide complexation by EDTA and DTPA in lactate media.

PubMed

Nash, K L; Brigham, D; Shehee, T C; Martin, A

2012-12-28

The interaction of trivalent lanthanide and actinide cations with polyaminopolycarboxylic acid complexing agents in lactic acid buffer systems is an important feature of the chemistry of the TALSPEAK process for the separation of trivalent actinides from lanthanides. To improve understanding of metal ion coordination chemistry in this process, the results of an investigation of the kinetics of lanthanide complexation by ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA) and diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA) in 0.3 M lactic acid/0.3 M ionic strength solution are reported. Progress of the reaction was monitored using the distinctive visible spectral changes attendant to lanthanide complexation by the colorimetric indicator ligand Arsenazo III, which enables the experiment but plays no mechanistic role. Under the conditions of these experiments, the reactions occur in a time regime suitable for study by stopped-flow spectrophotometric techniques. Experiments have been conducted as a function of EDTA/DTPA ligand concentration, total lactic acid concentration, and pH. The equilibrium perturbation reaction proceeds as a first order approach to equilibrium over a wide range of conditions, allowing the simultaneous determination of complex formation and dissociation rate constants. The rate of the complexation reaction has been determined for the entire lanthanide series (except Pm(3+)). The predominant pathway for lanthanide-EDTA and lanthanide-DTPA dissociation is inversely dependent on the total lactate concentration; the complex formation reaction demonstrates a direct dependence on [H(+)]. Unexpectedly, the rate of the complex formation reaction is seen in both ligand systems to be fastest for Gd(3+). Correlation of these results indicates that in 0.3 M lactate solutions the exchange of lanthanide ions between lactate complexes and the polyaminopolycarboxylate govern the process.

Antimicrobial Activity of Chitosan Film Forming Solution Enriched with Essential Oils; an in Vitro Assay

PubMed Central

Raphaël, Kana Jean; Meimandipour, Amir

2017-01-01

Background: The resistance of the bacteria and fungi to the innumerous antimicrobial agents is a major challenge in the treatment of the infections demands to the necessity for searching and finding new sources of substances with antimicrobial properties. The incorporation of the essential oils (EOs) in chitosan film forming solution may enhance antimicrobial properties. However, its use as the feeding additive in the poultry nutrition needs to clarify the product’s activity against both pathogen and the useful microbes in the gastrointestinal tract. Objectives: In the present study, we carried out an in vitro investigation and evaluated the antimicrobial activity of chitosan film forming solution incorporated with essential oils (CFs+EOs) against microbial strains including Staphylococcus aureus, Escherichia coli, Enterococcus faecium, Lactobacillus rahmnosus, Aspergillus niger and Alternaria alternate. Material and Methods: In three replicates, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of different treatments including: 1- essential oils (EOs), 2- chitosan film solution (CFs), and 3-chitosan film solution enriched with EOs (CFs+EOs) were determined against above mentioned microbes. Results: The results indicated that the chitosan solution enriched with essential oils (CFs+EOs) is capable of inhibiting the bacterial and fungal growth even at the lowest concentrations. The MIC and MBC for all the antimicrobial agents against Escherichia coli and Staphylococcus aureus were very low compared to the concentrations needed to inhibit the growth of useful bacteria, Lactobacillus rahmnosu and Enterococcus faecium. The antifungal activity of chitosan was enhanced as the concentration of EOs increased in the film solution. Conclusion: Chitosan-EOs complexes are the promising candidate for novel contact antimicrobial agents that can be used in animal feeds. PMID:29845058

Antimicrobial Activity of Chitosan Film Forming Solution Enriched with Essential Oils; an in Vitro Assay.

PubMed

Raphaël, Kana Jean; Meimandipour, Amir

2017-01-01

Background: The resistance of the bacteria and fungi to the innumerous antimicrobial agents is a major challenge in the treatment of the infections demands to the necessity for searching and finding new sources of substances with antimicrobial properties. The incorporation of the essential oils (EOs) in chitosan film forming solution may enhance antimicrobial properties. However, its use as the feeding additive in the poultry nutrition needs to clarify the product's activity against both pathogen and the useful microbes in the gastrointestinal tract. Objectives: In the present study, we carried out an in vitro investigation and evaluated the antimicrobial activity of chitosan film forming solution incorporated with essential oils (CFs+EOs) against microbial strains including Staphylococcus aureus, Escherichia coli, Enterococcus faecium, Lactobacillus rahmnosus, Aspergillus niger and Alternaria alternate . Material and Methods: In three replicates, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of different treatments including: 1- essential oils (EOs), 2- chitosan film solution (CFs), and 3-chitosan film solution enriched with EOs (CFs+EOs) were determined against above mentioned microbes. Results: The results indicated that the chitosan solution enriched with essential oils (CFs+EOs) is capable of inhibiting the bacterial and fungal growth even at the lowest concentrations. The MIC and MBC for all the antimicrobial agents against Escherichia coli and Staphylococcus aureus were very low compared to the concentrations needed to inhibit the growth of useful bacteria, Lactobacillus rahmnosu and Enterococcus faecium . The antifungal activity of chitosan was enhanced as the concentration of EOs increased in the film solution. Conclusion: Chitosan-EOs complexes are the promising candidate for novel contact antimicrobial agents that can be used in animal feeds.

Characterization of the host-guest complex of a curcumin analog with β-cyclodextrin and β-cyclodextrin-gemini surfactant and evaluation of its anticancer activity.

PubMed

Poorghorban, Masoomeh; Das, Umashankar; Alaidi, Osama; Chitanda, Jackson M; Michel, Deborah; Dimmock, Jonathan; Verrall, Ronald; Grochulski, Pawel; Badea, Ildiko

2015-01-01

Curcumin analogs, including the novel compound NC 2067, are potent cytotoxic agents that suffer from poor solubility, and hence, low bioavailability. Cyclodextrin-based carriers can be used to encapsulate such agents. In order to understand the interaction between the two molecules, the physicochemical properties of the host-guest complexes of NC 2067 with β-cyclodextrin (CD) or β-cyclodextrin-gemini surfactant (CDgemini surfactant) were investigated for the first time. Moreover, possible supramolecular structures were examined in order to aid the development of new drug delivery systems. Furthermore, the in vitro anticancer activity of the complex of NC 2067 with CDgemini surfactant nanoparticles was demonstrated in the A375 melanoma cell line. Physicochemical properties of the complexes formed of NC 2067 with CD or CDgemini surfactant were investigated by synchrotron-based powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Synchrotron-based small- and wide-angle X-ray scattering and size measurements were employed to assess the supramolecular morphology of the complex formed by NC 2067 with CDgemini surfactant. Lastly, the in vitro cell toxicity of the formulations toward A375 melanoma cells at various drug-to-carrier mole ratios were measured by cell viability assay. Physical mixtures of NC 2067 and CD or CDgemini surfactant showed characteristics of the individual components, whereas the complex of NC 2067 and CD or CDgemini surfactant presented new structural features, supporting the formation of the host-guest complexes. Complexes of NC 2067 with CDgemini surfactants formed nanoparticles having sizes of 100-200 nm. NC 2067 retained its anticancer activity in the complex with CDgemini surfactant for different drug-to-carrier mole ratios, with an IC50 (half-maximal inhibitory concentration) value comparable to that for NC 2067 without the carrier. The formation of host-guest complexes of NC 2067 with CD or CDgemini surfactant has been confirmed and hence the CDgemini surfactant shows good potential to be used as a delivery system for anticancer agents.

Characterization of the host–guest complex of a curcumin analog with β-cyclodextrin and β-cyclodextrin–gemini surfactant and evaluation of its anticancer activity

PubMed Central

Poorghorban, Masoomeh; Das, Umashankar; Alaidi, Osama; Chitanda, Jackson M; Michel, Deborah; Dimmock, Jonathan; Verrall, Ronald; Grochulski, Pawel; Badea, Ildiko

2015-01-01

Background Curcumin analogs, including the novel compound NC 2067, are potent cytotoxic agents that suffer from poor solubility, and hence, low bioavailability. Cyclodextrin-based carriers can be used to encapsulate such agents. In order to understand the interaction between the two molecules, the physicochemical properties of the host–guest complexes of NC 2067 with β-cyclodextrin (CD) or β-cyclodextrin–gemini surfactant (CDgemini surfactant) were investigated for the first time. Moreover, possible supramolecular structures were examined in order to aid the development of new drug delivery systems. Furthermore, the in vitro anticancer activity of the complex of NC 2067 with CDgemini surfactant nanoparticles was demonstrated in the A375 melanoma cell line. Methods Physicochemical properties of the complexes formed of NC 2067 with CD or CDgemini surfactant were investigated by synchrotron-based powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Synchrotron-based small- and wide-angle X-ray scattering and size measurements were employed to assess the supramolecular morphology of the complex formed by NC 2067 with CDgemini surfactant. Lastly, the in vitro cell toxicity of the formulations toward A375 melanoma cells at various drug-to-carrier mole ratios were measured by cell viability assay. Results Physical mixtures of NC 2067 and CD or CDgemini surfactant showed characteristics of the individual components, whereas the complex of NC 2067 and CD or CDgemini surfactant presented new structural features, supporting the formation of the host–guest complexes. Complexes of NC 2067 with CDgemini surfactants formed nanoparticles having sizes of 100–200 nm. NC 2067 retained its anticancer activity in the complex with CDgemini surfactant for different drug-to-carrier mole ratios, with an IC50 (half-maximal inhibitory concentration) value comparable to that for NC 2067 without the carrier. Conclusion The formation of host–guest complexes of NC 2067 with CD or CDgemini surfactant has been confirmed and hence the CDgemini surfactant shows good potential to be used as a delivery system for anticancer agents. PMID:25609956

Iron chelation as a possible mechanism for aspirin-induced malondialdehyde production by mouse liver microsomes and mitochondria.

PubMed Central

Schwarz, K B; Arey, B J; Tolman, K; Mahanty, S

1988-01-01

To investigate the possibility that lipid peroxidation is the mechanism responsible for aspirin-induced liver damage, pure neutralized acetylsalicylic acid (ASA), 0.6-90.9 mM, was added to calcium-aggregated mouse liver microsomes followed by incubation in NADPH buffer at 37 degrees C for 60 min and subsequent measurement of malondialdehyde (MDA). MDA production at ASA concentrations from 1.2 to 4.6 mM was greater than control (P less than 0.004). Peak MDA values were observed with 4.6 mM ASA, 39.58 +/- 6.73 nmol MDA/mg protein vs. 16.16 +/- 2.85 (P less than 0.004). Higher concentrations of ASA were inhibitory compared with the value at 4.6 mM (P less than 0.001). Aspirin had similar effects on MDA production by mouse liver mitochondria. MDA production with either ASA or buffer was completely suppressed by the potent iron-chelating agents desferrioxamine and alpha,alpha' dipyridyl when these were added to the microsomal preparations. Since MDA production in this system is known to be affected by iron-chelating agents (enhanced at low concentration, inhibited at higher concentration), the iron-chelating properties of ASA were investigated. Conductivity titration curves of Fe(OH)3 added to water or ASA suggested that the ASA was complexing with iron. The presence of an iron-ASA complex was established by high pressure liquid chromatographic analysis of the solution from this study. We conclude that aspirin enhances MDA production by hepatic microsomes and mitochondria via an aspirin-iron chelate and that this represents at least one mechanism by which aspirin may produce liver damage. PMID:3335633

Recovery of precious metals from space

NASA Technical Reports Server (NTRS)

Freiser, Henry

1991-01-01

The overall objective is to develop efficient and economical separation and recovery methods for the platinum group and other precious metals. The separation of Pd(II) from Pt(II), Ir(III), and Rh(III) with trioctylphosphine oxide (TOPO) in heptane using centrifugal partition chromatography (CPC) was investigated. Activities to achieve this objective focussed on selection and evaluation of extraction systems for the PGM and modification of selected systems for multistage operation with a view to scaling up to desired macro levels. On the basis of preliminary evaluation of a series of simple metal complexing agents and chelating agents, the TOPO in heptane was selected as a likely system for isolating of Pd(II) and Pt(II) from the other PGM. A multistage apparatus capable of configuration as a simple rugged device, a centrifugal partition chromatograph (CPC), was shown to be effective. The extraction of Pd(II) was studied by CPC and batch solvent extraction. The distribution ratios for Pd(II) determined by both methods agree well. In low HCl concentrations (less than 0.1 M), the extracted species was PdCl2.(TOPO)2, irrespective of the chloride concentration, while at acid concentrations above 0.1 M, the Pd was extracted as the ion pair, 2(TOPO.H+).(PdCl4)2-. Base line separation of Pd(II) and Pt(II) in CPC was obtained under a variety of chloride and HCl concentration. It was demonstrated that the efficiency of CPC for metal separation was limited by chemical kinetic factors rather than instrumental factors, strongly suggesting that dramatic improvements can be achieved by studying reaction kinetics of formation and dissociation of the extractable metal complex.

The highly intelligent virtual agents for modeling financial markets

NASA Astrophysics Data System (ADS)

Yang, G.; Chen, Y.; Huang, J. P.

2016-02-01

Researchers have borrowed many theories from statistical physics, like ensemble, Ising model, etc., to study complex adaptive systems through agent-based modeling. However, one fundamental difference between entities (such as spins) in physics and micro-units in complex adaptive systems is that the latter are usually with high intelligence, such as investors in financial markets. Although highly intelligent virtual agents are essential for agent-based modeling to play a full role in the study of complex adaptive systems, how to create such agents is still an open question. Hence, we propose three principles for designing high artificial intelligence in financial markets and then build a specific class of agents called iAgents based on these three principles. Finally, we evaluate the intelligence of iAgents through virtual index trading in two different stock markets. For comparison, we also include three other types of agents in this contest, namely, random traders, agents from the wealth game (modified on the famous minority game), and agents from an upgraded wealth game. As a result, iAgents perform the best, which gives a well support for the three principles. This work offers a general framework for the further development of agent-based modeling for various kinds of complex adaptive systems.

Used tire recycling to produce granulates: evaluation of occupational exposure to chemical agents.

PubMed

Savary, Barbara; Vincent, Raymond

2011-10-01

Exposure was assessed in four facilities where used tires are turned into rubber granulates. Particulate exposure levels were measured using filter samples and gravimetric analysis. In parallel, volatile organic compounds (VOCs) screening was carried out using samples taken on activated carbon supports, followed by an analysis using a gas chromatograph coupled to a spectrometric detector. The exposure level medians are between 0.58 and 3.95 mg m(-3). Clogging of the textile fiber separation systems can lead to worker exposure; in this case, the measured concentrations can reach 41 mg m(-3). However, in contrast to the data in the literature, VOC levels >1 p.p.m. were not detected. The particulate mixtures deposited on the installation surfaces are complex; some of the chemical agents are toxic to humans. The results of this study indicate significant exposure to complex mixtures of rubber dust. Optimizing exhaust ventilation systems inside the shredders, with a cyclone for example, is essential for reducing the exposure of workers in this rapidly developing sector.

Effects of iron(III)chelates on the solubility of heavy metals in calcareous soils.

PubMed

Ylivainio, Kari

2010-10-01

In this study I evaluated the effects of complexing agents on the solubility of heavy metals in an incubation experiment up to 56 days when complexing agents were applied as Fe-chelates (Fe-EDDS(S,S), Fe-EDDS(mix), Fe-EDTA and Fe-EDDHA) on calcareous soils at a level sufficient to correct Fe chlorosis (0.1 mmol kg(-1)). Of these ligands, EDDHA was the most efficient in keeping Fe in water-soluble form, and EDDS increased the solubility of Cu and Zn most, and only EDTA increased the solubility of Cd and Pb. EDTA increased the solubility of Ni steadily during the incubation period, equalling about 5-8% of the added EDTA concentration. [S,S]-EDDS was biodegraded within 56 days, whereas EDDS(mix) was less biodegradable. Ni-chelates were the most recalcitrant against biodegradation. The study shows that even a moderate input of chelates to soil increases the solubility of toxic heavy metals and their risk of leaching. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Grafting of a novel gold(III) complex on nanoporous MCM-41 and evaluation of its toxicity in Saccharomyces cerevisiae.

PubMed

Fazaeli, Yousef; Amini, Mostafa M; Ashourion, Hamed; Heydari, Homayoun; Majdabadi, Abbas; Jalilian, Amir Reza; Abolmaali, Shamsozoha

2011-01-01

The goal of this research was to investigate the potential of newly synthesized gold complex trichloro(2,4,6-trimethylpyridine)Au(III) as an anticancer agent. The gold(III) complex was synthesized and grafted on nanoporous silica, MCM-41, to produce AuCl(3)@PF-MCM- 41 (AuCl(3) grafted on pyridine-functionalized MCM-41). The toxicity of trichloro(2,4,6- trimethylpyridine)Au(III) and AuCl(3)@PF-MCM-41 in Saccharomyces cerevisiae (as a model system) was studied. The gold(III) complex showed a mid cytotoxic effect on yeast viability. Using the drug delivery system, nanoporous MCM-41, the gold(III) complex became a strong inhibitor for growth of yeast cells at a very low concentration. Furthermore, the animal tests revealed a high uptake of AuCl(3)@PF-MCM-41 in tumor cells. The stability of the compound was confirmed in human serum.

Detection and isolation of nucleic acid sequences using competitive hybridization probes

DOEpatents

Lucas, Joe N.; Straume, Tore; Bogen, Kenneth T.

1997-01-01

A method for detecting a target nucleic acid sequence in a sample is provided using hybridization probes which competitively hybridize to a target nucleic acid. According to the method, a target nucleic acid sequence is hybridized to first and second hybridization probes which are complementary to overlapping portions of the target nucleic acid sequence, the first hybridization probe including a first complexing agent capable of forming a binding pair with a second complexing agent and the second hybridization probe including a detectable marker. The first complexing agent attached to the first hybridization probe is contacted with a second complexing agent, the second complexing agent being attached to a solid support such that when the first and second complexing agents are attached, target nucleic acid sequences hybridized to the first hybridization probe become immobilized on to the solid support. The immobilized target nucleic acids are then separated and detected by detecting the detectable marker attached to the second hybridization probe. A kit for performing the method is also provided.

Detection and isolation of nucleic acid sequences using competitive hybridization probes

DOEpatents

Lucas, J.N.; Straume, T.; Bogen, K.T.

1997-04-01

A method for detecting a target nucleic acid sequence in a sample is provided using hybridization probes which competitively hybridize to a target nucleic acid. According to the method, a target nucleic acid sequence is hybridized to first and second hybridization probes which are complementary to overlapping portions of the target nucleic acid sequence, the first hybridization probe including a first complexing agent capable of forming a binding pair with a second complexing agent and the second hybridization probe including a detectable marker. The first complexing agent attached to the first hybridization probe is contacted with a second complexing agent, the second complexing agent being attached to a solid support such that when the first and second complexing agents are attached, target nucleic acid sequences hybridized to the first hybridization probe become immobilized on to the solid support. The immobilized target nucleic acids are then separated and detected by detecting the detectable marker attached to the second hybridization probe. A kit for performing the method is also provided. 7 figs.

Risks of using EDTA as an agent for trace metals dosing in anaerobic digestion of olive mill solid waste.

PubMed

Serrano, A; Pinto-Ibieta, F; Braga, A F M; Jeison, D; Borja, R; Fermoso, F G

2017-12-01

Low concentrations of trace elements in many organic wastes recommend their supplementation in order to avoid potential limitations. Different chelating agents have been used to ensure an adequate trace metal pool in the soluble fraction, by forming dissolved complexes. Ethylenediaminetetraacetic acid (EDTA) is probably the most common, although several negative effects could be associated with its usage. Biomethane potential tests were performed using Olive Mill Solid Waste as the substrate, supplementing different combinations of Fe, Co, Ni, Ba, always under the presence of EDTA. Results show that Ni and Co slightly recovered biodegradability. However, Ba supplementation resulted in worsening the methane yield coefficient in all cases. High concentration of EDTA led to decrease in the activity of anaerobic digestion. High availability of EDTA induces the capture of trace metals like Co or Ni, key trace metals for anaerobic biomass activity. While supplementing trace metals, the addition of Ba and/or EDTA must be carefully considered.

Synthesis and growth mechanism of sponge-like nickel using a hydrothermal method

NASA Astrophysics Data System (ADS)

Shao, Bin; Yin, Xueguo; Hua, Weidong; Ma, Yilong; Sun, Jianchun; Li, Chunhong; Chen, Dengming; Guo, Donglin; Li, Kejian

2018-05-01

Sponge-like nickel composed of micro-chains with a diameter of 1-5 μm was selectively synthesized by the hydrothermal method, using sodium hydroxide (NaOH) as the alkaline reagent, aqueous hydrazine as reducing agent and citric acid as a coordination agent. The time-dependent samples prepared at different NaOH concentrations were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectrometer (FTIR). The results showed that the agglomerates of nickel citrate hydrazine complex nanoplates were first precipitated and then reduced to prickly nickel micro-chains at a lower NaOH concentration, which played a role in the further formation of sponge-like nickel. Also, the probable growth mechanism of the sponge-like nickel was proposed. The magnetic properties of sponge-like nickel were studied using a vibrating sample magnetometer. The sponge-like nickel exhibited a ferromagnetic behavior with a saturation magnetization value of 43.8 emu g-1 and a coercivity value of 120.7 Oe.

Reduction of paraquat-induced renal cytotoxicity by manganese and copper complexes of EGTA and EHPG.

PubMed

Samai, Mohamed; Hague, Theresa; Naughton, Declan P; Gard, Paul R; Chatterjee, Prabal K

2008-02-15

Superoxide anion generation plays an important role in the development of paraquat toxicity. Although superoxide dismutase mimetics (SODm) have provided protection against organ injury involving generation of superoxide anions, they often suffer problems, e.g., regarding their bioavailability or potential pro-oxidant activity. The aim here was to investigate and compare the therapeutic potential of two novel SODm, manganese(II) and copper(II) complexes of the calcium chelator ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA) and of the contrast agent ethylenebis(hydroxyphenylglycine) (EHPG), against paraquat-induced renal toxicity in vitro. Incubation of renal NRK-52E cells with paraquat (1 mM) for 24 h produced submaximal, yet significant, reduction in cellular viability and cell death and produced significant increases in superoxide anion and hydroxyl radical generation. Manganese and copper complexes of EGTA (10-100 microM) and EHPG (30-100 microM) reduced paraquat-induced renal cell toxicity and reduced superoxide anion and hydroxyl radical generation significantly. Manganese complexes displayed greater efficacy than copper complexes and, at equivalent concentrations, manganese complexed with EHPG provided the greatest protection. Furthermore, these metal complexes did not interfere with the uptake of [methyl-(14)C]paraquat into NRK-52E cells, suggesting that they provided protection against paraquat cytotoxicity via intracellular mechanisms. These complexes did not display cytotoxicity at the concentrations examined. Together, these results suggest that manganese and copper complexes of EGTA and EHPG, and especially the manganese-EHPG complex, could provide benefit against paraquat nephrotoxicity.

Quantification of the interceptor action of caffeine on the in vitro biological effect of the anti-tumour agent topotecan.

PubMed

Evstigneev, M P; Mosunov, A A; Evstigneev, V P; Parkes, H G; Davies, D B

2011-08-01

Using published in vitro data on the dependence of the percentage of apoptosis induced by the anti-cancer drug topotecan in a leukaemia cell line on the concentration of added caffeine, and a general model of competitive binding in a system containing two aromatic drugs and DNA, it has been shown to be possible to quantify the relative change in the biological effect just using a set of component concentrations and equilibrium constants of the complexation of the drugs. It is also proposed that a general model of competitive binding and parameterization of that model may potentially be applied to any system of DNA-targeting aromatic drugs under in vitro conditions. The main reasons underpinning the proposal are the general feature of the complexation of aromatic drugs with DNA and their interaction in physiological media via hetero-association.

Fitness landscapes, heuristics and technological paradigms: A critique on random search models in evolutionary economics

NASA Astrophysics Data System (ADS)

Frenken, Koen

2001-06-01

The biological evolution of complex organisms, in which the functioning of genes is interdependent, has been analyzed as "hill-climbing" on NK fitness landscapes through random mutation and natural selection. In evolutionary economics, NK fitness landscapes have been used to simulate the evolution of complex technological systems containing elements that are interdependent in their functioning. In these models, economic agents randomly search for new technological design by trial-and-error and run the risk of ending up in sub-optimal solutions due to interdependencies between the elements in a complex system. These models of random search are legitimate for reasons of modeling simplicity, but remain limited as these models ignore the fact that agents can apply heuristics. A specific heuristic is one that sequentially optimises functions according to their ranking by users of the system. To model this heuristic, a generalized NK-model is developed. In this model, core elements that influence many functions can be distinguished from peripheral elements that affect few functions. The concept of paradigmatic search can then be analytically defined as search that leaves core elements in tact while concentrating on improving functions by mutation of peripheral elements.

Antibacterial Behavior of Additively Manufactured Porous Titanium with Nanotubular Surfaces Releasing Silver Ions.

PubMed

Amin Yavari, S; Loozen, L; Paganelli, F L; Bakhshandeh, S; Lietaert, K; Groot, J A; Fluit, A C; Boel, C H E; Alblas, J; Vogely, H C; Weinans, H; Zadpoor, A A

2016-07-13

Additive manufacturing (3D printing) has enabled fabrication of geometrically complex and fully interconnected porous biomaterials with huge surface areas that could be used for biofunctionalization to achieve multifunctional biomaterials. Covering the huge surface area of such porous titanium with nanotubes has been already shown to result in improved bone regeneration performance and implant fixation. In this study, we loaded TiO2 nanotubes with silver antimicrobial agents to equip them with an additional biofunctionality, i.e., antimicrobial behavior. An optimized anodizing protocol was used to create nanotubes on the entire surface area of direct metal printed porous titanium scaffolds. The nanotubes were then loaded by soaking them in three different concentrations (i.e., 0.02, 0.1, and 0.5 M) of AgNO3 solution. The antimicrobial behavior and cell viability of the developed biomaterials were assessed. As far as the early time points (i.e., up to 1 day) are concerned, the biomaterials were found to be extremely effective in preventing biofilm formation and decreasing the number of planktonic bacteria particularly for the middle and high concentrations of silver ions. Interestingly, nanotubes not loaded with antimicrobial agents also showed significantly smaller numbers of adherent bacteria at day 1, which may be attributed to the bactericidal effect of high aspect ratio nanotopographies. The specimens with the highest concentrations of antimicrobial agents adversely affected cell viability at day 1, but this effect is expected to decrease or disappear in the following days as the rate of release of silver ions was observed to markedly decrease within the next few days. The antimicrobial effects of the biomaterials, particularly the ones with the middle and high concentrations of antimicrobial agents, continued until 2 weeks. The potency of the developed biomaterials in decreasing the number of planktonic bacteria and hindering the formation of biofilms make them promising candidates for combating peri-operative implant-associated infections.

Antibacterial Potential of an Antimicrobial Agent Inspired by Peroxidase-Catalyzed Systems

PubMed Central

Tonoyan, Lilit; Fleming, Gerard T. A.; Mc Cay, Paul H.; Friel, Ruairi; O'Flaherty, Vincent

2017-01-01

Antibiotic resistance is an increasingly serious threat to global health. Consequently, the development of non-antibiotic based therapies and disinfectants, which avoid induction of resistance, or cross-resistance, is of high priority. We report the synthesis of a biocidal complex, which is produced by the reaction between ionic oxidizable salts—iodide and thiocyanate—in the presence of hydrogen peroxide as an oxidation source. The reaction generates bactericidal reactive oxygen and iodine species. In this study, we report that the iodo-thiocyanate complex (ITC) is an effective bactericidal agent with activity against planktonic and biofilm cells of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and methicillin-resistant S. aureus) bacteria. The minimum bactericidal concentrations and the minimum biofilm eradication concentrations of the biocidal composite were in the range of 7.8–31.3 and 31.3–250 μg ml−1, respectively. As a result, the complex was capable to cause a rapid cell death of planktonic test cultures at between 0.5 and 2 h, and complete eradication of dual and mono-species biofilms between 30 s and 10 min. Furthermore, the test bacteria, including a MRSA strain, exposed to the cocktail failed to develop resistance after serial passages. The antimicrobial activity of the ITC appears to derive from the combinational effect of the powerful species capable of oxidizing the essential biomolecules of bacteria. The use of this composition may provide an effective and efficient method for killing potential pathogens, as well as for disinfecting and removing biofilm contamination. PMID:28512449

Assessing bioavailability levels of metals in effluent-affected rivers: effect of Fe(III) and chelating agents on the distribution of metal speciation.

PubMed

Han, Shuping; Naito, Wataru; Masunaga, Shigeki

To assess the effects of Fe(III) and anthropogenic ligands on the bioavailability of Ni, Cu, Zn, and Pb, concentrations of bioavailable metals were measured by the DGT (diffusive gradients in thin films) method in some urban rivers, and were compared with concentrations calculated by a chemical equilibrium model (WHAM 7.0). Assuming that dissolved Fe(III) (<0.45 μm membrane filtered) was in equilibrium with colloidal iron oxide, the WHAM 7.0 model estimated that bioavailable concentrations of Ni, Cu, and Zn were slightly higher than the corresponding values estimated assuming that dissolved Fe(III) was absent. In contrast, lower levels of free Pb were predicted by the WHAM 7.0 model when dissolved Fe(III) was included. Estimates showed that most of the dissolved Pb was present as colloidal iron-Pb complex. Ethylene-diamine-tetra-acetic acid (EDTA) concentrations at sampling sites were predicted from the relationship between EDTA and the calculated bioavailable concentration of Zn. When both colloidal iron and predicted EDTA concentrations were included in the WHAM 7.0 calculations, dissolved metals showed a strong tendency to form EDTA complexes, in the order Ni > Cu > Zn > Pb. With the inclusion of EDTA, bioavailable concentrations of Ni, Cu, and Zn predicted by WHAM 7.0 were different from those predicted considering only humic substances and colloidal iron.

Pattern-oriented modeling of agent-based complex systems: Lessons from ecology

USGS Publications Warehouse

Grimm, Volker; Revilla, Eloy; Berger, Uta; Jeltsch, Florian; Mooij, Wolf M.; Railsback, Steven F.; Thulke, Hans-Hermann; Weiner, Jacob; Wiegand, Thorsten; DeAngelis, Donald L.

2005-01-01

Agent-based complex systems are dynamic networks of many interacting agents; examples include ecosystems, financial markets, and cities. The search for general principles underlying the internal organization of such systems often uses bottom-up simulation models such as cellular automata and agent-based models. No general framework for designing, testing, and analyzing bottom-up models has yet been established, but recent advances in ecological modeling have come together in a general strategy we call pattern-oriented modeling. This strategy provides a unifying framework for decoding the internal organization of agent-based complex systems and may lead toward unifying algorithmic theories of the relation between adaptive behavior and system complexity.

Pattern-Oriented Modeling of Agent-Based Complex Systems: Lessons from Ecology

NASA Astrophysics Data System (ADS)

Grimm, Volker; Revilla, Eloy; Berger, Uta; Jeltsch, Florian; Mooij, Wolf M.; Railsback, Steven F.; Thulke, Hans-Hermann; Weiner, Jacob; Wiegand, Thorsten; DeAngelis, Donald L.

2005-11-01

Agent-based complex systems are dynamic networks of many interacting agents; examples include ecosystems, financial markets, and cities. The search for general principles underlying the internal organization of such systems often uses bottom-up simulation models such as cellular automata and agent-based models. No general framework for designing, testing, and analyzing bottom-up models has yet been established, but recent advances in ecological modeling have come together in a general strategy we call pattern-oriented modeling. This strategy provides a unifying framework for decoding the internal organization of agent-based complex systems and may lead toward unifying algorithmic theories of the relation between adaptive behavior and system complexity.

Effect of high- or low-concentration bleaching agents containing calcium and/or fluoride on enamel microhardness.

PubMed

Furlan, Isabella Spinardi; Bridi, Enrico Coser; Amaral, Flávia Lucisano Botelho do; França, Fabiana Mantovani Gomes; Turssi, Cecilia Pedroso; Basting, Roberta Tarkany

2017-01-01

The aim of this in vitro study was to evaluate enamel microhardness following bleaching treatments using either high- or low-concentration hydrogen peroxide (HP) agents containing calcium and/or fluoride. Sixty enamel blocks were bleached with 1 of 6 different bleaching agents (n = 10). The high-concentration HP agents were Whiteness HP Maxx (35% HP), Whiteness HP Blue (35% HP, 2% calcium gluconate), Pola Office+ (37.5% HP, 5% potassium nitrate), and Opalescence Boost (38% HP, 1.1% fluoride ion, 3% potassium nitrate). The low-concentration HP agents evaluated were Pola Day (9.5% HP) and White Class (10% HP, potassium nitrate, calcium, fluoride). High-concentration agents were applied in 3 sessions, whereas low-concentration agents were applied for 14 days. Knoop microhardness measurements were taken on the surface of the enamel before bleaching, at various timepoints during bleaching, and 14 days after the final bleaching treatment. The 2-way analysis of variance test showed that microhardness values were significantly influenced by the bleaching agent (P < 0.001) and application time (P < 0.001). The Tukey test showed that enamel bleached with Whiteness HP Maxx or White Class presented lower microhardness values than did the enamel treated with the remaining products. There was a reduction in micro-hardness values up to the end of the treatment. The results showed that the composition, concentration, and application protocol for each bleaching agent influenced the enamel microhardness values in that the microhardness decreased over time, regardless of the agent used or the addition of calcium and/or fluoride.

Evaluation of "shotgun" proteomics for identification of biological threat agents in complex environmental matrixes: experimental simulations.

PubMed

Verberkmoes, Nathan C; Hervey, W Judson; Shah, Manesh; Land, Miriam; Hauser, Loren; Larimer, Frank W; Van Berkel, Gary J; Goeringer, Douglas E

2005-02-01

There is currently a great need for rapid detection and positive identification of biological threat agents, as well as microbial species in general, directly from complex environmental samples. This need is most urgent in the area of homeland security, but also extends into medical, environmental, and agricultural sciences. Mass-spectrometry-based analysis is one of the leading technologies in the field with a diversity of different methodologies for biothreat detection. Over the past few years, "shotgun"proteomics has become one method of choice for the rapid analysis of complex protein mixtures by mass spectrometry. Recently, it was demonstrated that this methodology is capable of distinguishing a target species against a large database of background species from a single-component sample or dual-component mixtures with relatively the same concentration. Here, we examine the potential of shotgun proteomics to analyze a target species in a background of four contaminant species. We tested the capability of a common commercial mass-spectrometry-based shotgun proteomics platform for the detection of the target species (Escherichia coli) at four different concentrations and four different time points of analysis. We also tested the effect of database size on positive identification of the four microbes used in this study by testing a small (13-species) database and a large (261-species) database. The results clearly indicated that this technology could easily identify the target species at 20% in the background mixture at a 60, 120, 180, or 240 min analysis time with the small database. The results also indicated that the target species could easily be identified at 20% or 6% but could not be identified at 0.6% or 0.06% in either a 240 min analysis or a 30 h analysis with the small database. The effects of the large database were severe on the target species where detection above the background at any concentration used in this study was impossible, though the three other microbes used in this study were clearly identified above the background when analyzed with the large database. This study points to the potential application of this technology for biological threat agent detection but highlights many areas of needed research before the technology will be useful in real world samples.

Determination of rhodium in metallic alloy and water samples using cloud point extraction coupled with spectrophotometric technique

NASA Astrophysics Data System (ADS)

Kassem, Mohammed A.; Amin, Alaa S.

2015-02-01

A new method to estimate rhodium in different samples at trace levels had been developed. Rhodium was complexed with 5-(4‧-nitro-2‧,6‧-dichlorophenylazo)-6-hydroxypyrimidine-2,4-dione (NDPHPD) as a complexing agent in an aqueous medium and concentrated by using Triton X-114 as a surfactant. The investigated rhodium complex was preconcentrated with cloud point extraction process using the nonionic surfactant Triton X-114 to extract rhodium complex from aqueous solutions at pH 4.75. After the phase separation at 50 °C, the surfactant-rich phase was heated again at 100 °C to remove water after decantation and the remaining phase was dissolved using 0.5 mL of acetonitrile. Under optimum conditions, the calibration curve was linear for the concentration range of 0.5-75 ng mL-1 and the detection limit was 0.15 ng mL-1 of the original solution. The enhancement factor of 500 was achieved for 250 mL samples containing the analyte and relative standard deviations were ⩽1.50%. The method was found to be highly selective, fairly sensitive, simple, rapid and economical and safely applied for rhodium determination in different complex materials such as synthetic mixture of alloys and environmental water samples.

ON THE REACTION OF COMPONENETS IN MeNO$sub 3$-UO$sub 2$(NO$sub 3$)$sub 2$- H$sub 2$O TYPE SYSTEMS (in Russian)

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

Yakimov, M.A.; Nosova, N.F.; Degtyarev, A.Ya.

1963-01-01

Solubility in ternary systems TlNO/sub 3/--UO/sub 2/(NO/sub 3/)/sub 2/-- H/sub 2/ O and CsNO/sub 3/--UO/sub 2/(NO/sub 3/)/sub 2/--H/sub 2/O at 0 to 25 c- C was studi ed by the isothermal method. The first system did not form solid phase compounds; the second system formed two compounds Cs/sub 2/UO/ sub 2/(NO/sub 3/)/sub 4/ and CsUO/sub 2/(NO/sub 3/)/sub 3/ at 25 c- and of water vapor pressure over the systems at 25 c- showed that water activity in the ternary systems at certain concentrations does not exceed the water activity in binary uranyl nitratewater system (at identical uranyl nitrate concentrations) confirmingmore » the observed complex formation in the solution. The mechanism of complex formation was analyzed and expanded for alkali metal - metal salt-complexing agent water systems. (R.V.J.)« less

Carbohydrate-Based Host-Guest Complexation of Hydrophobic Antibiotics for the Enhancement of Antibacterial Activity.

PubMed

Jeong, Daham; Joo, Sang-Woo; Shinde, Vijay Vilas; Cho, Eunae; Jung, Seunho

2017-08-08

Host-guest complexation with various hydrophobic drugs has been used to enhance the solubility, permeability, and stability of guest drugs. Physical changes in hydrophobic drugs by complexation have been related to corresponding increases in the bioavailability of these drugs. Carbohydrates, including various derivatives of cyclodextrins, cyclosophoraoses, and some linear oligosaccharides, are generally used as host complexation agents in drug delivery systems. Many antibiotics with low bioavailability have some limitations to their clinical use due to their intrinsically poor aqueous solubility. Bioavailability enhancement is therefore an important step to achieve the desired concentration of antibiotics in the treatment of bacterial infections. Antibiotics encapsulated in a complexation-based drug delivery system will display improved antibacterial activity making it possible to reduce dosages and overcome the serious global problem of antibiotic resistance. Here, we review the present research trends in carbohydrate-based host-guest complexation of various hydrophobic antibiotics as an efficient delivery system to improve solubility, permeability, stability, and controlled release.

Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents.

PubMed

Abengózar, María Ángeles; Cebrián, Rubén; Saugar, José María; Gárate, Teresa; Valdivia, Eva; Martínez-Bueno, Manuel; Maqueda, Mercedes; Rivas, Luis

2017-04-01

We report the feasibility of enterocin AS-48, a circular cationic peptide produced by Enterococcus faecalis , as a new leishmanicidal agent. AS-48 is lethal to Leishmania promastigotes as well as to axenic and intracellular amastigotes at low micromolar concentrations, with scarce cytotoxicity to macrophages. AS-48 induced a fast bioenergetic collapse of L. donovani promastigotes but only a partial permeation of their plasma membrane with limited entrance of vital dyes, even at concentrations beyond its full lethality. Fluoresceinated AS-48 was visualized inside parasites by confocal microscopy and seen to cause mitochondrial depolarization and reactive oxygen species production. Altogether, AS-48 appeared to have a mixed leishmanicidal mechanism that includes both plasma membrane permeabilization and additional intracellular targets, with mitochondrial dysfunctionality being of special relevance. This complex leishmanicidal mechanism of AS-48 persisted even for the killing of intracellular amastigotes, as evidenced by transmission electron microscopy. We demonstrated the potentiality of AS-48 as a new and safe leishmanicidal agent, expanding the growing repertoire of eukaryotic targets for bacteriocins, and our results provide a proof of mechanism for the search of new leishmanicidal bacteriocins, whose diversity constitutes an almost endless source for new structures at moderate production cost and whose safe use on food preservation is well established. Copyright © 2017 American Society for Microbiology.

Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents

PubMed Central

Abengózar, María Ángeles; Cebrián, Rubén; Saugar, José María; Gárate, Teresa; Valdivia, Eva; Martínez-Bueno, Manuel; Maqueda, Mercedes

2017-01-01

ABSTRACT We report the feasibility of enterocin AS-48, a circular cationic peptide produced by Enterococcus faecalis, as a new leishmanicidal agent. AS-48 is lethal to Leishmania promastigotes as well as to axenic and intracellular amastigotes at low micromolar concentrations, with scarce cytotoxicity to macrophages. AS-48 induced a fast bioenergetic collapse of L. donovani promastigotes but only a partial permeation of their plasma membrane with limited entrance of vital dyes, even at concentrations beyond its full lethality. Fluoresceinated AS-48 was visualized inside parasites by confocal microscopy and seen to cause mitochondrial depolarization and reactive oxygen species production. Altogether, AS-48 appeared to have a mixed leishmanicidal mechanism that includes both plasma membrane permeabilization and additional intracellular targets, with mitochondrial dysfunctionality being of special relevance. This complex leishmanicidal mechanism of AS-48 persisted even for the killing of intracellular amastigotes, as evidenced by transmission electron microscopy. We demonstrated the potentiality of AS-48 as a new and safe leishmanicidal agent, expanding the growing repertoire of eukaryotic targets for bacteriocins, and our results provide a proof of mechanism for the search of new leishmanicidal bacteriocins, whose diversity constitutes an almost endless source for new structures at moderate production cost and whose safe use on food preservation is well established. PMID:28167557

In vitro susceptibility of Staphylococcus aureus strains isolated from cows with subclinical mastitis to different antimicrobial agents

PubMed Central

Schlenker, Gerd; Szabo, Istvan; Roesler, Uwe

2012-01-01

Sensitivity to commercial teat dips (nonoxinol-9 iodine complex and chlorhexidine digluconate) of 56 Staphylococcus (S.) aureus strains isolated from quarter milk samples of various German dairy herds treated with different teat dipping schemes was investigated in this study. The minimum inhibitory concentration was determined using a broth macrodilution method according to the German Veterinary Association guidelines. The main objective of the current study was to induce in vitro resistance induction of S. aureus to chemical disinfectants. Ten different strains were repeatedly passed ten times in growth media with sub-lethal concentrations of disinfectants. Nine strains showed a significant reduction in susceptibility to the nonoxinol-9 iodine complex but only one strain developed resistance to chlorhexidine digluconate. Stability of the acquired resistance was observed in all S. aureus strains adapted to the nonoxinol-9 iodine complex and chlorhexidine digluconate. In contrast, simultaneous resistance to different antibiotics was not observed in any of the ten investigated S. aureus strains. However, the isolates exhibited a high degree of resistance to penicillin G. Based on these results, resistance of S. aureus to chemical disinfectants may be more likely to develop if the chemicals are used at concentrations lower than that required for an optimal biocidal effect. PMID:22705737

The complexity of minocycline serum protein binding.

PubMed

Zhou, Jian; Tran, Brian T; Tam, Vincent H

2017-06-01

Serum protein binding is critical for understanding the pharmacology of antimicrobial agents. Tigecycline and eravacycline were previously reported to have atypical non-linear protein binding; the percentage of free fraction decreased with increasing total concentration. In this study, we extended the investigation to other tetracyclines and examined the factors that might impact protein binding. Different minocycline concentrations (0.5-50 mg/L) and perfusion media (saline, 0.1 M HEPES buffer and 0.1 and 1 M PBS) were examined by in vitro microdialysis. After equilibration, two dialysate samples were taken from each experiment and the respective antimicrobial agent concentrations were analysed by validated LC-MS/MS methods. For comparison, the serum protein bindings of doxycycline and levofloxacin were also determined. The free fraction of minocycline decreased with increasing total concentration, and the results depended on the perfusion media used. The trends of minocycline protein binding in mouse and human sera were similar. In addition, serum protein binding of doxycycline showed the same concentration-dependent trend as minocycline, while the results of levofloxacin were concentration independent. The serum protein bindings of minocycline and doxycycline are negatively correlated with their total concentrations. It is possible that all tetracyclines share the same pharmacological property. Moreover, the specific perfusion media used could also impact the results of microdialysis. Additional studies are warranted to understand the mechanism(s) and clinical implications of serum protein binding of tetracyclines. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dynamic Nuclear Polarization NMR in Human Cells Using Fluorescent Polarizing Agents.

PubMed

Albert, Brice J; Gao, Chukun; Sesti, Erika L; Saliba, Edward P; Alaniva, Nicholas; Scott, Faith J; Sigurdsson, Snorri Th; Barnes, Alexander B

2018-06-20

Solid-state nuclear magnetic resonance (NMR) enables atomic resolution characterization of molecular structure and dynamics within complex heterogeneous samples, but it is typically insensitive. Dynamic nuclear polarization (DNP) increases NMR signal intensity by orders of magnitude and can be performed in combination with magic angle spinning (MAS) for sensitive, high-resolution spectroscopy. Here we report MAS DNP experiments, for the first time, within intact human cells with >40-fold DNP enhancement and a sample temperature below 6 K. In addition to cryogenic MAS results below 6 K, we also show in-cell DNP enhancements of 57-fold at 90 K. In-cell DNP is demonstrated using biradicals and sterically-shielded monoradicals as polarizing agents. A novel trimodal polarizing agent is introduced for DNP, which contains a nitroxide biradical, a targeting peptide for cell penetration, and a fluorophore for subcellular localization with confocal microscopy. The fluorescent polarizing agent provides in-cell DNP enhancements of 63-fold at a concentration of 2.7 mM. These experiments pave the way for structural characterization of biomolecules in an endogenous cellular context.

Quantifying cancer cell receptors with paired-agent fluorescent imaging: a novel method to account for tissue optical property effects

NASA Astrophysics Data System (ADS)

Sadeghipour, Negar; Davis, Scott C.; Tichauer, Kenneth M.

2018-02-01

Dynamic fluorescence imaging approaches can be used to estimate the concentration of cell surface receptors in vivo. Kinetic models are used to generate the final estimation by taking the targeted imaging agent concentration as a function of time. However, tissue absorption and scattering properties cause the final readout signal to be on a different scale than the real fluorescent agent concentration. In paired-agent imaging approaches, simultaneous injection of a suitable control imaging agent with a targeted one can account for non-specific uptake and retention of the targeted agent. Additionally, the signal from the control agent can be a normalizing factor to correct for tissue optical property differences. In this study, the kinetic model used for paired-agent imaging analysis (i.e., simplified reference tissue model) is modified and tested in simulation and experimental data in a way that accounts for the scaling correction within the kinetic model fit to the data to ultimately extract an estimate of the targeted biomarker concentration.

Biomedical properties of a series of ruthenium-N-heterocyclic carbene complexes based on oxidant activity in vitro and assessment in vivo of biosafety in zebrafish embryos.

PubMed

Alfaro, Juan M; Prades, Amparo; del Carmen Ramos, María; Peris, Eduardo; Ripoll-Gómez, Jorge; Poyatos, Macarena; Burgos, Javier S

2010-03-01

N-Heterocyclic carbene (NHC) ligands have attracted great interest over the last decade for their use in the design of homogenous catalysts. NHC-based metal complexes have interesting potential biomedical applications, such as in antimicrobial and cancer therapy, which are beginning to be explored more fully. We have studied here the oxidant activities of a series of Ru(II) complexes in vitro and zebrafish (Danio rerio) have been used as a model in vivo to investigate and characterize the toxicity of some of these compounds. Dual behavior was observed for the NHC-based complexes as they behaved as antioxidants at low concentrations but showed pro-oxidant capacity at higher concentrations. Zebrafish embryos were exposed to Ru(II) complexes under several different conditions (0 or 24 h postfertilization, with or without the chorion) and various parameters, such as viability, edema, heart rate, blood coagulation, pigmentation, scoliosis, malformation, and hatching, were tested. In general, zebrafish embryos were not harmed by exposure to Ru(II) complexes whatever the experimental conditions. Several toxicity profiles were observed depending upon the chemical structure of the compound in question. Their characteristics as pro-oxidant and/or antioxidant agents together with their biosafety may point to their having biomedical applications as antitumoral or neuroprotective drugs.

Spectrophotometric determination of flucloxacillin in pharmaceutical preparations using some nitrophenols as a complexing agent

NASA Astrophysics Data System (ADS)

El-Mammli, Magda Y.

2003-03-01

Some nitrophenols are proposed as chromogenic reagents for the spectrophotometric determination of flucloxacillin. The reagent forms a greenish yellow 1:1 complex with flucloxacillin at pH 9.0. This complex is stable for at least 3.0 h after its formation. The greenish yellow charge transfer complex species has an absorption maximum at 446, 435, 442, 473 and 439 nm for p-nitrophenol (I), 2,4-dinitrophenol (II), 3,5-dinitrosalycilic acid (III), picramic acid (IV) and picric acid (V), respectively, with a molar absorptivity between 1.43×10 4 and 2.59×10 4 l mol -1 cm -1. Beer's low is valid over the concentration range 2.0-40 μg ml -1 of flucloxacillin. The detection and quantitation limits as well as relative standard deviation were also calculated. The reagents have been successfully used for the spectrophotometric determination of flucloxacillin in pure form and in pharmaceutical preparations.

Oxidative phosphorylation-dependent regulation of cancer cell apoptosis in response to anticancer agents.

PubMed

Yadav, N; Kumar, S; Marlowe, T; Chaudhary, A K; Kumar, R; Wang, J; O'Malley, J; Boland, P M; Jayanthi, S; Kumar, T K S; Yadava, N; Chandra, D

2015-11-05

Cancer cells tend to develop resistance to various types of anticancer agents, whether they adopt similar or distinct mechanisms to evade cell death in response to a broad spectrum of cancer therapeutics is not fully defined. Current study concludes that DNA-damaging agents (etoposide and doxorubicin), ER stressor (thapsigargin), and histone deacetylase inhibitor (apicidin) target oxidative phosphorylation (OXPHOS) for apoptosis induction, whereas other anticancer agents including staurosporine, taxol, and sorafenib induce apoptosis in an OXPHOS-independent manner. DNA-damaging agents promoted mitochondrial biogenesis accompanied by increased accumulation of cellular and mitochondrial ROS, mitochondrial protein-folding machinery, and mitochondrial unfolded protein response. Induction of mitochondrial biogenesis occurred in a caspase activation-independent mechanism but was reduced by autophagy inhibition and p53-deficiency. Abrogation of complex-I blocked DNA-damage-induced caspase activation and apoptosis, whereas inhibition of complex-II or a combined deficiency of OXPHOS complexes I, III, IV, and V due to impaired mitochondrial protein synthesis did not modulate caspase activity. Mechanistic analysis revealed that inhibition of caspase activation in response to anticancer agents associates with decreased release of mitochondrial cytochrome c in complex-I-deficient cells compared with wild type (WT) cells. Gross OXPHOS deficiencies promoted increased release of apoptosis-inducing factor from mitochondria compared with WT or complex-I-deficient cells, suggesting that cells harboring defective OXPHOS trigger caspase-dependent as well as caspase-independent apoptosis in response to anticancer agents. Interestingly, DNA-damaging agent doxorubicin showed strong binding to mitochondria, which was disrupted by complex-I-deficiency but not by complex-II-deficiency. Thapsigargin-induced caspase activation was reduced upon abrogation of complex-I or gross OXPHOS deficiency whereas a reverse trend was observed with apicidin. Together, these finding provide a new strategy for differential mitochondrial targeting in cancer therapy.

Bifunctional chelating agent for the design and development of site specific radiopharmaceuticals and biomolecule conjugation strategy

DOEpatents

Katti, Kattesh V.; Prabhu, Kandikere R.; Gali, Hariprasad; Pillarsetty, Nagavara Kishore; Volkert, Wynn A.

2003-10-21

There is provided a method of labeling a biomolecule with a transition metal or radiometal in a site specific manner to produce a diagnostic or therapeutic pharmaceutical compound by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radio metal or a transition metal, and covalently linking the resulting metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. Also provided is a method of synthesizing the --PR.sub.2 containing biomolecules by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radiometal or a transition metal, and covalently linking the resulting radio metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. There is provided a therapeutic or diagnostic agent comprising a --PR.sub.2 containing biomolecule.

Effects of iodinated contrast agent, xylocaine and gadolinium concentration on the signal emitted in magnetic resonance arthrography: a samples study*

PubMed Central

da Silva, Yvana Lopes Pinheiro; Costa, Rita Zanlorensi Visneck; Pinho, Kátia Elisa Prus; Ferreira, Ricardo Rabello; Schuindt, Sueliton Miyamoto

2015-01-01

Objective To investigate the effects of dilution of paramagnetic contrast agent with iodinated contrast and xylocaine on the signal intensity during magnetic resonance arthrography, and to improve the paramagnetic contrast agent concentration utilized in this imaging modality. Materials and Methods Samples specially prepared for the study with three different concentrations of paramagnetic contrast agent diluted in saline, iodinated contrast agent and xylocaine were imaged with fast spin echo T1-weighted sequences with fat saturation. The samples were placed into flasks and graphical analysis of the signal intensity was performed as a function of the paramagnetic contrast concentration. Results As compared with samples of equal concentrations diluted only with saline, the authors have observed an average signal intensity decrease of 20.67% for iodinated contrast agent, and of 28.34% for xylocaine. However, the increased gadolinium concentration in the samples caused decrease in signal intensity with all the dilutions. Conclusion Minimizing the use of iodinated contrast media and xylocaine and/or the use of a gadolinium concentration of 2.5 mmol/L diluted in saline will improve the sensitivity of magnetic resonance arthrography. PMID:25987746

Differential effect of buffering agents on the crystallization of gemcitabine hydrochloride in frozen solutions.

PubMed

Patel, Mehulkumar; Munjal, Bhushan; Bansal, Arvind K

2014-08-25

The purpose of this study was to evaluate the differential effect of buffering agents on the crystallization of gemcitabine hydrochloride (GHCl) in frozen solutions. Four buffering agents, viz. citric acid (CA), malic acid (MA), succinic acid (SA) and tartaric acid (TA) were selected and their effect on GHCl crystallization was monitored using standard DSC and low temperature XRD. Onset of GHCl crystallization during heating run in DSC was measured to compare the differential effect of buffering agents. Glass transition temperature (Tg'), unfrozen water content in the freeze concentrate and crystallization propensity of the buffering agents was also determined for mechanistic understanding of the underlying effects. CA and MA inhibited while SA facilitated crystallization of GHCl even at 25 mM concentration. Increasing the concentration enhanced their effect. However, TA inhibited GHCl crystallization at concentrations <100mM and facilitated it at concentrations ≥100 mM. Lyophilization of GHCl with either SA or TA yielded elegant cakes, while CA and MA caused collapse. Tg' failed to explain the inhibitory effects of CA, MA and TA as all buffering agents lowered the Tg' of the system. Differential effect of buffering agents on GHCl crystallization could be explained by consideration of two opposing factors: (i) their own crystallization tendency and (ii) unfrozen water content in the freeze concentrate. In conclusion, it was established that API crystallization in frozen solution is affected by the type and concentration of the buffering agents. Copyright © 2014 Elsevier B.V. All rights reserved.

Technetium-99m generator system

DOEpatents

Mirzadeh, Saed; Knapp, Jr., Furn F.; Collins, Emory D.

1998-01-01

A .sup.99 Mo/.sup.99m Tc generator system includes a sorbent column loaded with a composition containing .sup.99 Mo. The sorbent column has an effluent end in fluid communication with an anion-exchange column for concentrating .sup.99m Tc eluted from the sorbent column. A method of preparing a concentrated solution of .sup.99m Tc includes the general steps of: a. providing a sorbent column loaded with a composition containing .sup.99 Mo, the sorbent column having an effluent end in fluid communication with an anion-exchange column; b. eluting the sorbent column with a salt solution to elute .sup.99m Tc from the sorbent and to trap and concentrate the eluted .sup.99m Tc on the ion-exchange column; and c. eluting the concentrated .sup.99m Tc from the ion-exchange column with a solution comprising a reductive complexing agent.

Technetium-99m generator system

DOEpatents

Mirzadeh, S.; Knapp, F.F. Jr.; Collins, E.D.

1998-06-30

A {sup 99}Mo/{sup 99m}Tc generator system includes a sorbent column loaded with a composition containing {sup 99}Mo. The sorbent column has an effluent end in fluid communication with an anion-exchange column for concentrating {sup 99m}Tc eluted from the sorbent column. A method of preparing a concentrated solution of {sup 99m}Tc includes the general steps of: (a) providing a sorbent column loaded with a composition containing {sup 99}Mo, the sorbent column having an effluent end in fluid communication with an anion-exchange column; (b) eluting the sorbent column with a salt solution to elute {sup 99m}Tc from the sorbent and to trap and concentrate the eluted {sup 99m}Tc on the ion-exchange column; and (c) eluting the concentrated {sup 99m}Tc from the ion-exchange column with a solution comprising a reductive complexing agent. 1 fig.

Spectrophotometric determination of dopaminergic drugs used for Parkinson's disease, cabergoline and ropinirole, in pharmaceutical preparations.

PubMed

Onal, Armağan; Cağlar, Sena

2007-04-01

Simple and reproducible spectrophotometric methods have been developed for determination of dopaminergic drugs used for Parkinson's disease, cabergoline (CAB) and ropinirole hydrochloride (ROP), in pharmaceutical preparations. The methods are based on the reactions between the studied drug substances and ion-pair agents [methyl orange (MO), bromocresol green (BCG) and bromophenol blue (BPB)] producing yellow colored ion-pair complexes in acidic buffers, after extracting in dichloromethane, which are spectrophotometrically determined at the appropriate wavelength of ion-pair complexes. Beer's law was obeyed within the concentration range from 1.0 to 35 microg ml(-1). The developed methods were applied successfully for the determination of these drugs in tablets.

Diffusion properties of conventional and calcium-sensitive MRI contrast agents in the rat cerebral cortex.

PubMed

Hagberg, Gisela E; Mamedov, Ilgar; Power, Anthony; Beyerlein, Michael; Merkle, Hellmut; Kiselev, Valerij G; Dhingra, Kirti; Kubìček, Vojtĕch; Angelovski, Goran; Logothetis, Nikos K

2014-01-01

Calcium-sensitive MRI contrast agents can only yield quantitative results if the agent concentration in the tissue is known. The agent concentration could be determined by diffusion modeling, if relevant parameters were available. We have established an MRI-based method capable of determining diffusion properties of conventional and calcium-sensitive agents. Simulations and experiments demonstrate that the method is applicable both for conventional contrast agents with a fixed relaxivity value and for calcium-sensitive contrast agents. The full pharmacokinetic time-course of gadolinium concentration estimates was observed by MRI before, during and after intracerebral administration of the agent, and the effective diffusion coefficient D* was determined by voxel-wise fitting of the solution to the diffusion equation. The method yielded whole brain coverage with a high spatial and temporal sampling. The use of two types of MRI sequences for sampling of the diffusion time courses was investigated: Look-Locker-based quantitative T(1) mapping, and T(1) -weighted MRI. The observation times of the proposed MRI method is long (up to 20 h) and consequently the diffusion distances covered are also long (2-4 mm). Despite this difference, the D* values in vivo were in agreement with previous findings using optical measurement techniques, based on observation times of a few minutes. The effective diffusion coefficient determined for the calcium-sensitive contrast agents may be used to determine local tissue concentrations and to design infusion protocols that maintain the agent concentration at a steady state, thereby enabling quantitative sensing of the local calcium concentration. Copyright © 2014 John Wiley & Sons, Ltd.

Maternal drug use: evaluation of risks to breast-fed infants.

PubMed

Kirksey, A; Groziak, S M

1984-01-01

This paper, based on a review of the literature, evaluates the risks to infants of maternal drug use during lactation. The potential harm of a particular drug to the breastfed infant is related both to the complex mechanism of milk synthesis and secretion and the mode of passage of the drug from plasma into milk. The 1st part of the paper discusses mammary cell and milk synthesis, milk secretion and composition, the mode of passage of drugs into milk, and factors influencing drug concentrations in milk. Drug concentrations in milk are dependent on 6 major factors: drug dosage, proportion bound in plasma, molecular weight, lipid solubility, degree of ionization, and pH difference between plasma and milk. Drugs that are weak acids are ionized to a greater extent and are more protein-bound than weak alkaline drugs. The 2nd part of the paper evaluates the risks to breastfed infants of selected pharmacons. Some categories of drugs that contain pharmacons that should be limited or avoided by nursing mothers are alkylating agents, analgesics and anti-inflammatory agents, anticoagulants, anticonvulsants, anti-infective agents, central nervous system stimulants, hormones, laxatives, minerals, provitamins, psychotherapeutic agents, thyroid affecting agents, and vitamins. The following precautions are suggested to minimize the risks of potentially harmful pharmacons: 1) all unnecessary medications should be avoided by nrusing mothers; 2) if medication is necessary during lactation, drug dosage should be controlled and the infant should be monitored for adverse symptoms; 3) drugs should be administered shortly after breastfeeding and the interval prolonged before the next feeding; and 4) if the infant must be fed soon after a potentially harmful drug has been taken by the mother, bottle feeding is recommended.

Novel cholinesterase modulators and their ability to interact with DNA

NASA Astrophysics Data System (ADS)

Janockova, Jana; Gulasova, Zuzana; Musilek, Kamil; Kuca, Kamil; Kozurkova, Maria

2013-11-01

In the present work, an interaction of four cholinesterase modulators (1-4) with calf thymus DNA was studied via spectroscopic techniques (UV-Vis, fluorescent spectroscopy and circular dichroism). From UV-Vis spectroscopic analysis, the binding constants for DNA-pyridinium oximes complexes were calculated (K = 3.5 × 104 to 1.4 × 105 M-1). All these measurements indicated that the compounds behave as effective DNA-interacting agents. Electrophoretic techniques proved that ligand 2 inhibited topoisomerase I at a concentration 5 μM.

Inorganic Nanoparticle as a Carrier for Hepatitis B Viral Capsids

NASA Astrophysics Data System (ADS)

Dekhtyar, Yu.; Romanova, M.; Kachanovska, A.; Skrastiņa, D.; Reinhofa, R.; Pumpens, P.; Patmalnieks, A.

Virus like particles (VLP) are used to transport immune response-modulating agents to target cells to treat them. In order to deliver a high concentration of VLP to the cell, a number of VLP can be attached to a nanoparticle to be used as a nanolorry. In this study, SiO2 nanoparticles were attached to Hepatitis B VLP. Spectrophotometry measurements, electron, and fluorescent microscopy evidence showed that the SiO2 - Hepatitis B VLP complexes were formed.

Biology Division progress report, October 1, 1983-September 30, 1984

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

Griesmer, R.A.

1985-01-01

The report provides summaries of the aims, scope and progress from October 1983 through September 1984. Major interest was focused on the health effects of neutron- and heavy-ion radiations on animals with particular attention to the carcinogenic responses to low dose levels and to the RBE of various forms of radiation. Among chemical agents, activities concentrated on evaluating and understanding the toxicological interations when mammals are exposed to complex mixtures, either concurrently or successively. Separate abstracts have been prepared for individual sections. (ACR)

Separation of compounds with multiple -OH groups from dilute aqueous solutions via complexation with organoboronate

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

Chow, Tina Kuo Fung

1992-05-01

The complexing extractant agent investigated in this work is 3-nitrophenylboronic acid (NPBA) in its anionic form (NPB). NPBA and Aliquat 336 (quaternary amine) is dissolved in 2-ethyl-l-hexanol, and the extractant is contacted with aq. NaOH. Solutes investigated were 1,2-propanediol, glycerol, fructose, sorbitol and lactic acid. Batch extraction experiments were performed at 25°C. Partition coefficients, distribution ratios and loadings are reported for varying concentrations of solute and NPB. All solutes complexed with NPB -, with all complexes containing only one NPB - per complex. The 1:1 complexation constants for the solutes glycerol, fructose and sorbitol follow trends similar to complexation withmore » B(OH) 4 - (aq.), i.e. the complexation constants increase with increasing number of -OH groups available for complexation. Assumption of 1:1 complex is not valid for 1, 2-propanediol, which showed overloading (more than one mole of solute complexed to one mole NPB -) at higher concentrations. The -OH group on the NPB - which is left uncomplexed after one solute molecule had bound to the other two -OH groups may be responsible for the overloading. Overloading is also observed in extraction of tactic acid, but through a different mechanism. It was found that TOMA + can extract lactic acid to an extent comparable to the uptake of lactic acid by NPB -. The complexation is probably through formation of an acid-base ion pair. Losses of NPBA into the aqueous phase could lead to problems, poor economics in industrial separation processes. One way of overcoming this problem would be to incorporate the NPBA onto a solid support.« less

Separation of compounds with multiple -OH groups from dilute aqueous solutions via complexation with organoboronate. [1,2-propanediol

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

Chow, Tina Kuo Fung.

1992-05-01

The complexing extractant agent investigated in this work is 3-nitrophenylboronic acid (NPBA) in its anionic form (NPB). NPBA and Aliquat 336 (quaternary amine) is dissolved in 2-ethyl-l-hexanol, and the extractant is contacted with aq. NaOH. Solutes investigated were 1,2-propanediol, glycerol, fructose, sorbitol and lactic acid. Batch extraction experiments were performed at 25{degree}C. Partition coefficients, distribution ratios and loadings are reported for varying concentrations of solute and NPB. All solutes complexed with NPB{sup {minus}}, with all complexes containing only one NPB{sup {minus}} per complex. The 1:1 complexation constants for the solutes glycerol, fructose and sorbitol follow trends similar to complexation withmore » B(OH){sub 4}{sup {minus}} (aq.), i.e. the complexation constants increase with increasing number of {minus}OH groups available for complexation. Assumption of 1:1 complex is not valid for 1, 2-propanediol, which showed overloading (more than one mole of solute complexed to one mole NPB{sup {minus}}) at higher concentrations. The {minus}OH group on the NPB{sup {minus}} which is left uncomplexed after one solute molecule had bound to the other two {minus}OH groups may be responsible for the overloading. Overloading is also observed in extraction of tactic acid, but through a different mechanism. It was found that TOMA{sup +} can extract lactic acid to an extent comparable to the uptake of lactic acid by NPB{sup {minus}}. The complexation is probably through formation of an acid-base ion pair. Losses of NPBA into the aqueous phase could lead to problems, poor economics in industrial separation processes. One way of overcoming this problem would be to incorporate the NPBA onto a solid support.« less

[Evaluation of the sanitary-and-epidemiological safety of flocculating agents used for portable water purification].

PubMed

Zholdakova, Z I; Sinitsyna, O O; Tul'skaia, E A

2006-01-01

Polyelectrolytes used in the practice of water supply to the population were comparatively hygienically studied, by using a complex of hazard indices and a new approach to sanitary-and-epidemiological evaluation of the safety of water-soluble polymers is substantiated. The anionic and cationic flocculating agents from different chemical classes, such as Superflok A-100, Fennopol A 321E, Fennopol K 221E, Praestol 2530 TR, VPK-402, Superflok C-577, Saipan, KF-91, Ecosol-401, a low molecular-weight sodium polyacrylate were tested as model compounds. Moreover, the information already available in the scientific literature on the toxicity of synthetic polyelectrolytes was analyzed. The generalized maximum permissible concentrations were substantiated for individual chemical classes of synthetic polyelectrolytes: polyacrylamides, polyamines, polydiallyldimethylammonium chloride.

Concentration rather than dose defines the local brain toxicity of agents that are effectively distributed by convection-enhanced delivery.

PubMed

Zhang, Rong; Saito, Ryuta; Mano, Yui; Kanamori, Masayuki; Sonoda, Yukihiko; Kumabe, Toshihiro; Tominaga, Teiji

2014-01-30

Convection-enhanced delivery (CED) has been developed as a potentially effective drug-delivery strategy into the central nervous system. In contrast to systemic intravenous administration, local delivery achieves high concentration and prolonged retention in the local tissue, with increased chance of local toxicity, especially with toxic agents such as chemotherapeutic agents. Therefore, the factors that affect local toxicity should be extensively studied. With the assumption that concentration-oriented evaluation of toxicity is important for local CED, we evaluated the appearance of local toxicity among different agents after delivery with CED and studied if it is dose dependent or concentration dependent. Local toxicity profile of chemotherapeutic agents delivered via CED indicates BCNU was dose-dependent, whereas that of ACNU was concentration-dependent. On the other hand, local toxicity for doxorubicin, which is not distributed effectively by CED, was dose-dependent. Local toxicity for PLD, which is extensively distributed by CED, was concentration-dependent. Traditional evaluation of drug induced toxicity was dose-oriented. This is true for systemic intravascular delivery. However, with local CED, toxicity of several drugs exacerbated in concentration-dependent manner. From our study, local toxicity of drugs that are likely to distribute effectively tended to be concentration-dependent. Concentration rather than dose may be more important for the toxicity of agents that are effectively distributed by CED. Concentration-oriented evaluation of toxicity is more important for CED. Copyright © 2013 Elsevier B.V. All rights reserved.

Diagnostic nanoparticle targeting of the EGF-receptor in complex biological conditions using single-domain antibodies.

PubMed

Zarschler, K; Prapainop, K; Mahon, E; Rocks, L; Bramini, M; Kelly, P M; Stephan, H; Dawson, K A

2014-06-07

For effective localization of functionalized nanoparticles at diseased tissues such as solid tumours or metastases through biorecognition, appropriate targeting vectors directed against selected tumour biomarkers are a key prerequisite. The diversity of such vector molecules ranges from proteins, including antibodies and fragments thereof, through aptamers and glycans to short peptides and small molecules. Here, we analyse the specific nanoparticle targeting capabilities of two previously suggested peptides (D4 and GE11) and a small camelid single-domain antibody (sdAb), representing potential recognition agents for the epidermal growth factor receptor (EGFR). We investigate specificity by way of receptor RNA silencing techniques and look at increasing complexity in vitro by introducing increasing concentrations of human or bovine serum. Peptides D4 and GE11 proved problematic to employ and conjugation resulted in non-receptor specific uptake into cells. Our results show that sdAb-functionalized particles can effectively target the EGFR, even in more complex bovine and human serum conditions where targeting specificity is largely conserved for increasing serum concentration. In human serum however, an inhibition of overall nanoparticle uptake is observed with increasing protein concentration. For highly affine targeting ligands such as sdAbs, targeting a receptor such as EGFR with low serum competitor abundance, receptor recognition function can still be partially realised in complex conditions. Here, we stress the value of evaluating the targeting efficiency of nanoparticle constructs in realistic biological milieu, prior to more extensive in vivo studies.

New approaches in agent-based modeling of complex financial systems

NASA Astrophysics Data System (ADS)

Chen, Ting-Ting; Zheng, Bo; Li, Yan; Jiang, Xiong-Fei

2017-12-01

Agent-based modeling is a powerful simulation technique to understand the collective behavior and microscopic interaction in complex financial systems. Recently, the concept for determining the key parameters of agent-based models from empirical data instead of setting them artificially was suggested. We first review several agent-based models and the new approaches to determine the key model parameters from historical market data. Based on the agents' behaviors with heterogeneous personal preferences and interactions, these models are successful in explaining the microscopic origination of the temporal and spatial correlations of financial markets. We then present a novel paradigm combining big-data analysis with agent-based modeling. Specifically, from internet query and stock market data, we extract the information driving forces and develop an agent-based model to simulate the dynamic behaviors of complex financial systems.

Multi-Agent Strategic Modeling in a Specific Environment

NASA Astrophysics Data System (ADS)

Gams, Matjaz; Bezek, Andraz

Multi-agent modeling in ambient intelligence (AmI) is concerned with the following task [19]: How can external observations of multi-agent systems in the ambient be used to analyze, model, and direct agent behavior? The main purpose is to obtain knowledge about acts in the environment thus enabling proper actions of the AmI systems [1]. Analysis of such systems must thus capture complex world state representation and asynchronous agent activities. Instead of studying basic numerical data, researchers often use more complex data structures, such as rules and decision trees. Some methods are extremely useful when characterizing state space, but lack the ability to clearly represent temporal state changes occurred by agent actions. To comprehend simultaneous agent actions and complex changes of state space, most often a combination of graphical and symbolical representation performs better in terms of human understanding and performance.

Dithiothreitol abrogates the effect of arsenic trioxide on normal rat liver mitochondria and human hepatocellular carcinoma cells

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

Paul, Manash K.; Kumar, Rajinder; Mukhopadhyay, Anup K.

2008-01-15

Arsenic trioxide (ATO) is a known environmental toxicant and a potent chemotherapeutic agent. Significant correlation has been reported between consumption of arsenic-contaminated water and occurrence of liver cancer; moreover, ATO-treated leukemia patients also suffers from liver toxicity. Hence, modulation of ATO action may help to prevent populations suffering from arsenic toxicity as well as help reduce the drug-related side effects. Dithiothreitol (DTT) is a well-known dithiol agent reported to modulate the action of ATO. Controversial reports exist regarding the effect of DTT on ATO-induced apoptosis in leukemia cells. To the best of our knowledge, no report illustrates the modulatory effectmore » of DTT on ATO-induced liver toxicity, the prime target for arsenic. Mitochondria serve as the doorway to apoptosis and have been implicated in ATO-induced cell death. Hence, we attempted to study the modulatory effect of DTT on ATO-induced dysfunction of mammalian liver mitochondria and human hepatocellular carcinoma cell line (Hep3B). We, for the first time, report that ATO produces complex I-mediated electron transfer inhibition, reactive oxygen species (ROS) generation, respiration inhibition, and ATO-induced ROS-mediated mitochondrial permeability transition (MPT) opening. DTT at low concentration (100 {mu}M and less) prevents the effect of ATO-induced complex I-malfunctions. DTT protects mitochondria from ATO-mediated opening of MPT and membrane potential depolarization. DTT also prevented ATO-induced Hep3B cell death. Thus, at low concentrations DTT abrogates the effect of ATO on rat liver mitochondria and Hep3B cell line. Therefore, the present result suggests, that use of low concentration of dithiols as food supplement may prevent arsenic toxicity in affected population.« less

Two-Photon-Active Organotin(IV) Complexes for Antibacterial Function and Superresolution Bacteria Imaging.

PubMed

Hu, Lei; Wang, Hui; Xia, Tingting; Fang, Bin; Shen, Yu; Zhang, Qiong; Tian, Xiaohe; Zhou, Hongping; Wu, Jieying; Tian, Yupeng

2018-06-04

Antibacterial agents with two-photon absorption are expected to play a significant role in biomedical science. Herein, two novel organotin complexes, HLSn1 and HLSn2, based on coumarin were designed, synthesized, and systematically investigated. It was found that these complexes possessed suitable two-photon-active cross sections in the near-infrared region. Moreover, complex HLSn1 could efficiently inhibit the growth of Gram-negative Escherichia coli and Gram-positive Bacillus subtilis, especially the latter with a minimum inhibitory concentration (MIC; 90%) of 2 ± 0.14 μg mL -1 , which is lower than that of Kanamycin (Kana, 8 ± 0.42 μg mL -1 ). Importantly, two-photon imaging and superresolution development of bacterial stain revealed that complex HLSn1 can react with bacterial membranes, producing reactive oxygen species (ROS) and leading to cell death. These outcomes provide promising applications in the superresolution bacteria imaging, diagnostics, and treatment of bacterial infectious.

Membrane extraction with thermodynamically unstable diphosphonic acid derivatives

DOEpatents

Horwitz, Earl Philip; Gatrone, Ralph Carl; Nash, Kenneth LaVerne

1997-01-01

Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulphur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described.

Hydroxy double salts intercalated with Mn(II) complexes as potential contrast agents

NASA Astrophysics Data System (ADS)

Jin, Miao; Li, Wanjing; Spillane, Dominic E. M.; Geraldes, Carlos F. G. C.; Williams, Gareth R.; Bligh, S. W. Annie

2016-03-01

A series of Mn(II) aminophosphonate complexes were successfully synthesized and intercalated into the hydroxy double salt [Zn5(OH)8]Cl2·yH2O. Complex incorporation led to an increase in the interlayer spacing from 7.8 to 10-12 Å. Infrared spectroscopy showed the presence of the characteristic vibration peaks of the Mn(II) complexes in the intercalates' spectra, indicating successful incorporation. The complex-loaded composites had somewhat lower proton relaxivities than the pure complexes. Nevertheless, these intercalates may have use as MRI contrast agents for patients with poor kidney function, where traditional Gd(III)-based contrast agents cause severe renal failure.

Method and apparatus for enhanced detection of toxic agents

DOEpatents

Greenbaum, Elias; Rodriguez, Jr., Miguel; Wu, Jie Jayne; Qi, Hairong

2013-10-01

A biosensor based detection of toxins includes enhancing a fluorescence signal by concentrating a plurality of photosynthetic organisms in a fluid into a concentrated region using biased AC electro-osmosis. A measured photosynthetic activity of the photosynthetic organisms is obtained in the concentrated region, where chemical, biological or radiological agents reduce a nominal photosynthetic activity of the photosynthetic organisms. A presence of the chemical, biological and/or radiological agents or precursors thereof, is determined in the fluid based on the measured photosynthetic activity of the concentrated plurality of photosynthetic organisms. A lab-on-a-chip system is used for the concentrating step. The presence of agents is determined from feature vectors, obtained from processing a time dependent signal using amplitude statistics and/or time-frequency analysis, relative to a control signal. A linear discriminant method including support vector machine classification (SVM) is used to identify the agents.

Multi-Wavelength Photomagnetic Imaging for Oral Cancer

NASA Astrophysics Data System (ADS)

Marks, Michael

In this study, a multi-wavelength Photomagnetic Imaging (PMI) system is developed and evaluated with experimental studies.. PMI measures temperature increases in samples illuminated by near-infrared light sources using magnetic resonance thermometry. A multiphysics solver combining light and heat transfer models the spatiotemporal distribution of the temperature change. The PMI system develop in this work uses three lasers of varying wavelength (785 nm, 808 nm, 860 nm) to heat the sample. By using multiple wavelengths, we enable the PMI system to quantify the relative concentrations of optical contrast in turbid media and monitor their distribution, at a higher resolution than conventional diffuse optical imaging. The data collected from agarose phantoms with multiple embedded contrast agents designed to simulate the optical properties of oxy- and deoxy-hemoglobin is presented. The reconstructed images demonstrate that multi-wavelength PMI can resolve this complex inclusion structure with high resolution and recover the concentration of each contrast agent with high quantitative accuracy. The modified multi-wavelength PMI system operates under the maximum skin exposure limits defined by the American National Standards Institute, to enable future clinical applications.

Microfludic platforms for the evaluation of anti-platelet agent efficacy under hyper-shear conditions associated with ventricular assist devices.

PubMed

Dimasi, Annalisa; Rasponi, Marco; Consolo, Filippo; Fiore, Gianfranco B; Bluestein, Danny; Slepian, Marvin J; Redaelli, Alberto

2017-10-01

Thrombus formation is a major adverse event affecting patients implanted with ventricular assist devices (VADs). Despite anti-thrombotic drug administration, thrombotic events remain frequent within the first year post-implantation. Platelet activation (PA) is an essential process underling thrombotic adverse events in VAD systems. Indeed, abnormal shear forces, correlating with specific flow trajectories of VADs, are strong agonists mediating PA. To date, the ability to determine efficacy of anti-platelet (AP) agents under shear stress conditions is limited. Here, we present a novel microfluidic platform designed to replicate shear stress patterns of a clinical VAD, and use it to compare the efficacy of two AP agents in vitro. Gel-filtered platelets were incubated with i) acetylsalicylic acid (ASA) and ii) ticagrelor, at two different concentrations (ASA: 125 and 250 µM; ticagrelor: 250 and 500 nM) and were circulated in the VAD-emulating microfluidic platform using a peristaltic pump. GFP was collected after 4 and 52 repetitions of exposure to the VAD shear pattern and tested for shear-mediated PA. ASA significantly inhibited PA only at 2-fold higher concentration (250 µM) than therapeutic dose (125 µM). The effect of ticagrelor was not dependent on drug concentration, and did not show significant inhibition with respect to untreated control. This study demonstrates the potential use of microfluidic platforms as means of testing platelet responsiveness and AP drug efficacy under complex and realistic VAD-like shear stress conditions. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Chemotherapeutic response to cisplatin-like drugs in human breast cancer cells probed by vibrational microspectroscopy.

PubMed

Batista de Carvalho, A L M; Pilling, M; Gardner, P; Doherty, J; Cinque, G; Wehbe, K; Kelley, C; Batista de Carvalho, L A E; Marques, M P M

2016-06-23

Studies of drug-cell interactions in cancer model systems are essential in the preclinical stage of rational drug design, which relies on a thorough understanding of the mechanisms underlying cytotoxic activity and biological effects, at a molecular level. This study aimed at applying complementary vibrational spectroscopy methods to evaluate the cellular impact of two Pt(ii) and Pd(ii) dinuclear chelates with spermine (Pt2Spm and Pd2Spm), using cisplatin (cis-Pt(NH3)2Cl2) as a reference compound. Their effects on cellular metabolism were monitored in a human triple-negative metastatic breast cancer cell line (MDA-MB-231) by Raman and synchrotron-radiation infrared microspectroscopies, for different drug concentrations (2-8 μM) at 48 h exposure. Multivariate data analysis was applied (unsupervised PCA), unveiling drug- and concentration-dependent effects: apart from discrimination between control and drug-treated cells, a clear separation was obtained for the different agents studied - mononuclear vs. polynuclear, and Pt(ii) vs. Pd(ii). Spectral biomarkers of drug action were identified, as well as the cellular response to the chemotherapeutic insult. The main effect of the tested compounds was found to be on DNA, lipids and proteins, the Pd(ii) agent having a more significant impact on proteins while its Pt(ii) homologue affected the cellular lipid content at lower concentrations, which suggests the occurrence of distinct and unconventional pathways of cytotoxicity for these dinuclear polyamine complexes. Raman and FTIR microspectroscopies were confirmed as powerful non-invasive techniques to obtain unique spectral signatures of the biochemical impact and physiological reaction of cells to anticancer agents.

A functional form for injected MRI Gd-chelate contrast agent concentration incorporating recirculation, extravasation and excretion

NASA Astrophysics Data System (ADS)

Horsfield, Mark A.; Thornton, John S.; Gill, Andrew; Jager, H. Rolf; Priest, Andrew N.; Morgan, Bruno

2009-05-01

A functional form for the vascular concentration of MRI contrast agent after intravenous bolus injection was developed that can be used to model the concentration at any vascular site at which contrast concentration can be measured. The form is based on previous models of blood circulation, and is consistent with previously measured data at long post-injection times, when the contrast agent is fully and evenly dispersed in the blood. It allows the first-pass and recirculation peaks of contrast agent to be modelled, and measurement of the absolute concentration of contrast agent at a single time point allows the whole time course to be rescaled to give absolute contrast agent concentration values. This measure of absolute concentration could be performed at a long post-injection time using either MRI or blood-sampling methods. In order to provide a model that is consistent with measured data, it was necessary to include both rapid and slow extravasation, together with excretion via the kidneys. The model was tested on T1-weighted data from the descending aorta and hepatic portal vein, and on T*2-weighted data from the cerebral arteries. Fitting of the model was successful for all datasets, but there was a considerable variation in fit parameters between subjects, which suggests that the formation of a meaningful population-averaged vascular concentration function is precluded.

Enhancing Potentially Plant-Available Lead Concentrations in Contaminated Residential Soils Using a Biodegradable Chelating Agent

NASA Astrophysics Data System (ADS)

Andra, S.; Datta, R.; Sarkar, D.; Saminathan, S.

2007-12-01

Chelation of heavy metals is an important factor in enhancing metal solubility and, hence, metal availability to plants to promote phytoremediation. In the present study, we compared the effects of application of a biodegradable chelating agent, namely, ethylenediaminedisuccinic acid (EDDS) on enhancing plant available form of lead (Pb) in Pb-based paint contaminated residential soils compared to that of a more commonly used, but non-biodegradable chelate, i.e., ethylenediaminetetraacetic acid (EDTA). Development of a successful phytoremediation model for metals such as Pb depends on a thorough understanding of the physical and chemical properties of the soil, along with the optimization of a chelate treatment to mobilize Pb from `unavailable' pools to potentially plant available fraction. In this context, we set out to perform batch incubation experiments to investigate the effectiveness of the two aforementioned chelates in enhancing plant available Pb at four different concentrations (0, 5, 10 and 15 mM/kg soil) and three treatment durations (0, 10 and 30 days). We selected 12 contaminated residential soils from two major metropolitan areas (San Antonio, TX and Baltimore, MD) with varying soil physico-chemical properties - the soils from San Antonio were primarily alkaline and those from Baltimore were typically acidic. Total soil Pb concentrations ranged between 256 mg/kg and 4,182 mg/kg. Our results show that both chelates increased the solubility of Pb, otherwise occluded in the complex soil matrix. For both EDTA and EDDS, the exchangeable concentrations of soil Pb also increased with increase in chelate concentration and incubation time. The most effective treatment was 15 mM chelate kg-1 soil incubated for 30 days, which caused many fold increase in potentially plant available Pb (a combination of the soluble and exchangeable fractions) relative to the unamended controls. Step wise multiple linear regression analysis using chelate-extractable Pb and soil properties showed that plant available Pb fraction could be assessed from the two inter-related soil parameters: soil organic matter and soil pH. Although EDTA was more effective in Pb solubilization than EDDS, the rapid kinetics of the Pb-EDTA complexation process and the prolonged persistence of EDTA in soils pose a potential groundwater contamination problem via metal leaching. In contrast to EDTA, EDDS addition caused relatively slow release of Pb from the soil matrix. The biodegradable nature (and short half life) of EDDS in soils makes it a promising chelating agent for use as soil amendment to enhance Pb solubilization and hence, potential plant uptake.

Tissue Penetration of Antifungal Agents

PubMed Central

Felton, Timothy; Troke, Peter F.

2014-01-01

SUMMARY Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection. PMID:24396137

An Approach for Autonomy: A Collaborative Communication Framework for Multi-Agent Systems

NASA Technical Reports Server (NTRS)

Dufrene, Warren Russell, Jr.

2005-01-01

Research done during the last three years has studied the emersion properties of Complex Adaptive Systems (CAS). The deployment of Artificial Intelligence (AI) techniques applied to remote Unmanned Aerial Vehicles has led the author to investigate applications of CAS within the field of Autonomous Multi-Agent Systems. The core objective of current research efforts is focused on the simplicity of Intelligent Agents (IA) and the modeling of these agents within complex systems. This research effort looks at the communication, interaction, and adaptability of multi-agents as applied to complex systems control. The embodiment concept applied to robotics has application possibilities within multi-agent frameworks. A new framework for agent awareness within a virtual 3D world concept is possible where the vehicle is composed of collaborative agents. This approach has many possibilities for applications to complex systems. This paper describes the development of an approach to apply this virtual framework to the NASA Goddard Space Flight Center (GSFC) tetrahedron structure developed under the Autonomous Nano Technology Swarm (ANTS) program and the Super Miniaturized Addressable Reconfigurable Technology (SMART) architecture program. These projects represent an innovative set of novel concepts deploying adaptable, self-organizing structures composed of many tetrahedrons. This technology is pushing current applied Agents Concepts to new levels of requirements and adaptability.

Agent planning in AgScala

NASA Astrophysics Data System (ADS)

Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

2013-10-01

Agent-oriented programming languages are designed to simplify the development of software agents, especially those that exhibit complex, intelligent behavior. This paper presents recent improvements of AgScala, an agent-oriented programming language based on Scala. AgScala includes declarative constructs for managing beliefs, actions and goals of intelligent agents. Combined with object-oriented and functional programming paradigms offered by Scala, it aims to be an efficient framework for developing both purely reactive, and more complex, deliberate agents. Instead of the Prolog back-end used initially, the new version of AgScala relies on Agent Planning Package, a more advanced system for automated planning and reasoning.

Liposome encapsulation of chelating agents

DOEpatents

Rahman, Yueh Erh

1976-01-13

A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

Remediation of cadmium- and lead-contaminated agricultural soil by composite washing with chlorides and citric acid.

PubMed

Li, Yu-jiao; Hu, Peng-jie; Zhao, Jie; Dong, Chang-xun

2015-04-01

Composite washing of cadmium (Cd)- and lead (Pb)-contaminated agricultural soil from Hunan province in China using mixtures of chlorides (FeCl3, CaCl2) and citric acid (CA) was investigated. The concentrations of composite washing agents for metal removal were optimized. Sequential extraction was conducted to study the changes in metal fractions after soil washing. The removal of two metals at optimum concentration was reached. Using FeCl3 mixed with CA, 44% of Cd and 23% of Pb were removed, and 49 and 32% by CaCl2 mixed with CA, respectively. The mechanism of composite washing was postulated. A mixture of chlorides and CA enhanced metal extraction from soil through the formation of metal-chloride and metal-citrate complexes. CA in extract solutions promoted the formation of metal-chloride complexes and reduced the solution pH. Composite washing reduced Cd and Pb in Fe-Mn oxide forms significantly. Chlorides and CA exerted a synergistic effect on metal extraction during composite washing.

Positive Effect of Propolis on Free Radicals in Burn Wounds

PubMed Central

Olczyk, Pawel; Ramos, Pawel; Komosinska-Vassev, Katarzyna; Stojko, Jerzy; Pilawa, Barbara

2013-01-01

Concentration and properties of free radicals in the burn wounds treated with propolis were examined by the use of electron paramagnetic resonance spectroscopy. Magnetic spin-spin interactions and complex free radicals structures in wound beds were studied. The results were compared to those obtained for silver sulphadiazine used as a standard pharmaceutical agent. The changes of free radicals in the matrix of injury with time of exposition on these substances were tested. The aim of this study was to check the hypothesis about the best influence of propolis on the burn wounds healing. It was confirmed that a relatively lower concentration of free radicals exists in the burn wounds treated with propolis. The homogeneously broadened spectra and a complex free radical system characterize the tested tissue samples. The fastening of spin-lattice relaxation processes in the matrix of injury after treatment with propolis and silver sulphadiazine was observed. Practical usefulness of electron paramagnetic resonance spectroscopy in alternative medicine was proved. PMID:23762125

Intramitochondrial Ascorbic Acid Enhances the Formation of Mitochondrial Superoxide Induced by Peroxynitrite via a Ca2+-Independent Mechanism

PubMed Central

Guidarelli, Andrea; Cerioni, Liana; Fiorani, Mara; Cantoni, Orazio

2017-01-01

Exposure of U937 cells to peroxynitrite promotes mitochondrial superoxide formation via a mechanism dependent on both inhibition of complex III and increased mitochondrial Ca2+ accumulation. Otherwise inactive concentrations of the oxidant produced the same maximal effects in the presence of either complex III inhibitors or agents mobilizing Ca2+ from the ryanodine receptor and enforcing its mitochondrial accumulation. l-Ascorbic acid (AA) produced similar enhancing effects in terms of superoxide formation, DNA strand scission and cytotoxicity. However, AA failed to enhance the intra-mitochondrial concentration of Ca2+ and the effects observed in cells supplemented with peroxinitrite, while insensitive to manipulations preventing the mobilization of Ca2+, or the mitochondrial accumulation of the cation, were also detected in human monocytes and macrophages, which do not express the ryanodine receptor. In all these cell types, mitochondrial permeability transition-dependent toxicity was detected in cells exposed to AA/peroxynitrite and, based on the above criteria, these responses also appeared Ca2+-independent. The enhancing effects of AA are therefore similar to those mediated by bona fide complex III inhibitors, although the vitamin failed to directly inhibit complex III, and in fact enhanced its sensitivity to the inhibitory effects of peroxynitrite. PMID:28767071

[Interference for Various Quench Agents of Chemical Disinfectants on Detection of Endotoxin Activities in Water].

PubMed

Zhang, Can; Liu, Wen-jun; Shi, Yun; An, Dai-zhi; Bai, Miao; Xu, Wen

2015-05-01

The quenching agents such as histidine, glycine, ascorbic acid, Tween-80, sodium sulfite and sodium hyposulfite are commonly used for quenching the residual disinfectant in water. In this paper, in order to select the optimal type and concentration range of quenching agents prior to the Limulus assays, the interference effects of each quenching agent at different concentrations on endotoxin detection were investigated by the Limulus assays of kinetic-turbidity. Our results identified that, as for 0-1.0% concentration of histidine, ascorbic acid, Tween-80, sodium sulfite (pH unadjusted and pH neutral), interference on the Limulus assays was existed. Hence, these quenching agents could not be applied as neutralizers prior to Limulus assays. Although, there was no interference on endotoxin detection for the glycine, a yellow color, developed by the quenching products of glycine and glutaric dialdehyde, contributed to false positive results. Hence, glycine should not be used as quenching agents in Limulus assays for samples containing glutaric dialdehyde. Compared with other quenching agents as histidine, glycine, ascorbic acid, Tween-80, sodium sulfite, 0-1.0% concentration of sodium hyposulfite elicited no obvious interference, while 1.0%-5.0% concentration of sodium hyposulfite illustrated exhibition effect for endotoxin detection. All in all, compared with other quenching agents as histidine, glycine, ascorbic acid, Tween-80 and sodium sulfite, sodium hyposulfite is suitable for quenching chemicals prior to endotoxin detection and less than 0.5% of concentration is allowable.

Method for preparing radionuclide-labeled chelating agent-ligand complexes

DOEpatents

Meares, Claude F.; Li, Min; DeNardo, Sally J.

1999-01-01

Radionuclide-labeled chelating agent-ligand complexes that are useful in medical diagnosis or therapy are prepared by reacting a radionuclide, such as .sup.90 Y or .sup.111 In, with a polyfunctional chelating agent to form a radionuclide chelate that is electrically neutral; purifying the chelate by anion exchange chromatography; and reacting the purified chelate with a targeting molecule, such as a monoclonal antibody, to form the complex.

Biological and Clinical Aspects of Lanthanide Coordination Compounds

PubMed Central

Misra, Sudhindra N.; M., Indira Devi; Shukla, Ram S.

2004-01-01

The coordinating chemistry of lanthanides, relevant to the biological, biochemical and medical aspects, makes a significant contribution to understanding the basis of application of lanthanides, particularly in biological and medical systems. The importance of the applications of lanthanides, as an excellent diagnostic and prognostic probe in clinical diagnostics, and an anticancer material, is remarkably increasing. Lanthanide complexes based X-ray contrast imaging and lanthanide chelates based contrast enhancing agents for magnetic resonance imaging (MRI) are being excessively used in radiological analysis in our body systems. The most important property of the chelating agents, in lanthanide chelate complex, is its ability to alter the behaviour of lanthanide ion with which it binds in biological systems, and the chelation markedly modifies the biodistribution and excretion profile of the lanthanide ions. The chelating agents, especially aminopoly carboxylic acids, being hydrophilic, increase the proportion of their complex excreted from complexed lanthanide ion form biological systems. Lanthanide polyamino carboxylate-chelate complexes are used as contrast enhancing agents for Magnetic Resonance Imaging. Conjugation of antibodies and other tissue specific molecules to lanthanide chelates has led to a new type of specific MRI contrast agents and their conjugated MRI contrast agents with improved relaxivity, functioning in the body similar to drugs. Many specific features of contrast agent assisted MRI make it particularly effective for musculoskeletal and cerebrospinal imaging. Lanthanide-chelate contrast agents are effectively used in clinical diagnostic investigations involving cerebrospinal diseases and in evaluation of central nervous system. Chelated lanthanide complexes shift reagent aided 23Na NMR spectroscopic analysis is used in cellular, tissue and whole organ systems. PMID:18365075

Modeling the Internet of Things, Self-Organizing and Other Complex Adaptive Communication Networks: A Cognitive Agent-Based Computing Approach.

PubMed

Laghari, Samreen; Niazi, Muaz A

2016-01-01

Computer Networks have a tendency to grow at an unprecedented scale. Modern networks involve not only computers but also a wide variety of other interconnected devices ranging from mobile phones to other household items fitted with sensors. This vision of the "Internet of Things" (IoT) implies an inherent difficulty in modeling problems. It is practically impossible to implement and test all scenarios for large-scale and complex adaptive communication networks as part of Complex Adaptive Communication Networks and Environments (CACOONS). The goal of this study is to explore the use of Agent-based Modeling as part of the Cognitive Agent-based Computing (CABC) framework to model a Complex communication network problem. We use Exploratory Agent-based Modeling (EABM), as part of the CABC framework, to develop an autonomous multi-agent architecture for managing carbon footprint in a corporate network. To evaluate the application of complexity in practical scenarios, we have also introduced a company-defined computer usage policy. The conducted experiments demonstrated two important results: Primarily CABC-based modeling approach such as using Agent-based Modeling can be an effective approach to modeling complex problems in the domain of IoT. Secondly, the specific problem of managing the Carbon footprint can be solved using a multiagent system approach.

Determination of rhodium in metallic alloy and water samples using cloud point extraction coupled with spectrophotometric technique.

PubMed

Kassem, Mohammed A; Amin, Alaa S

2015-02-05

A new method to estimate rhodium in different samples at trace levels had been developed. Rhodium was complexed with 5-(4'-nitro-2',6'-dichlorophenylazo)-6-hydroxypyrimidine-2,4-dione (NDPHPD) as a complexing agent in an aqueous medium and concentrated by using Triton X-114 as a surfactant. The investigated rhodium complex was preconcentrated with cloud point extraction process using the nonionic surfactant Triton X-114 to extract rhodium complex from aqueous solutions at pH 4.75. After the phase separation at 50°C, the surfactant-rich phase was heated again at 100°C to remove water after decantation and the remaining phase was dissolved using 0.5mL of acetonitrile. Under optimum conditions, the calibration curve was linear for the concentration range of 0.5-75ngmL(-1) and the detection limit was 0.15ngmL(-1) of the original solution. The enhancement factor of 500 was achieved for 250mL samples containing the analyte and relative standard deviations were ⩽1.50%. The method was found to be highly selective, fairly sensitive, simple, rapid and economical and safely applied for rhodium determination in different complex materials such as synthetic mixture of alloys and environmental water samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Oxidative phosphorylation-dependent regulation of cancer cell apoptosis in response to anticancer agents

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

Yadav, N.; Kumar, S.; Marlowe, T.

Cancer cells tend to develop resistance to various types of anticancer agents, whether they adopt similar or distinct mechanisms to evade cell death in response to a broad spectrum of cancer therapeutics is not fully defined. Current study concludes that DNA-damaging agents (etoposide and doxorubicin), ER stressor (thapsigargin), and histone deacetylase inhibitor (apicidin) target oxidative phosphorylation (OXPHOS) for apoptosis induction, whereas other anticancer agents including staurosporine, taxol, and sorafenib induce apoptosis in an OXPHOS-independent manner. DNA-damaging agents promoted mitochondrial biogenesis accompanied by increased accumulation of cellular and mitochondrial ROS, mitochondrial protein-folding machinery, and mitochondrial unfolded protein response. Induction of mitochondrialmore » biogenesis occurred in a caspase activation-independent mechanism but was reduced by autophagy inhibition and p53-deficiency. Abrogation of complex-I blocked DNA-damage-induced caspase activation and apoptosis, whereas inhibition of complex-II or a combined deficiency of OXPHOS complexes I, III, IV, and V due to impaired mitochondrial protein synthesis did not modulate caspase activity. Mechanistic analysis revealed that inhibition of caspase activation in response to anticancer agents associates with decreased release of mitochondrial cytochrome c in complex-I-deficient cells compared with wild type (WT) cells. Gross OXPHOS deficiencies promoted increased release of apoptosis-inducing factor from mitochondria compared with WT or complex-I-deficient cells, suggesting that cells harboring defective OXPHOS trigger caspase-dependent as well as caspase-independent apoptosis in response to anticancer agents. Interestingly, DNA-damaging agent doxorubicin showed strong binding to mitochondria, which was disrupted by complex-I-deficiency but not by complex-II-deficiency. Thapsigargin-induced caspase activation was reduced upon abrogation of complex-I or gross OXPHOS deficiency whereas a reverse trend was observed with apicidin. Together, these finding provide a new strategy for differential mitochondrial targeting in cancer therapy.« less

Oxidative phosphorylation-dependent regulation of cancer cell apoptosis in response to anticancer agents

DOE PAGES

Yadav, N.; Kumar, S.; Marlowe, T.; ...

2015-11-05

Cancer cells tend to develop resistance to various types of anticancer agents, whether they adopt similar or distinct mechanisms to evade cell death in response to a broad spectrum of cancer therapeutics is not fully defined. Current study concludes that DNA-damaging agents (etoposide and doxorubicin), ER stressor (thapsigargin), and histone deacetylase inhibitor (apicidin) target oxidative phosphorylation (OXPHOS) for apoptosis induction, whereas other anticancer agents including staurosporine, taxol, and sorafenib induce apoptosis in an OXPHOS-independent manner. DNA-damaging agents promoted mitochondrial biogenesis accompanied by increased accumulation of cellular and mitochondrial ROS, mitochondrial protein-folding machinery, and mitochondrial unfolded protein response. Induction of mitochondrialmore » biogenesis occurred in a caspase activation-independent mechanism but was reduced by autophagy inhibition and p53-deficiency. Abrogation of complex-I blocked DNA-damage-induced caspase activation and apoptosis, whereas inhibition of complex-II or a combined deficiency of OXPHOS complexes I, III, IV, and V due to impaired mitochondrial protein synthesis did not modulate caspase activity. Mechanistic analysis revealed that inhibition of caspase activation in response to anticancer agents associates with decreased release of mitochondrial cytochrome c in complex-I-deficient cells compared with wild type (WT) cells. Gross OXPHOS deficiencies promoted increased release of apoptosis-inducing factor from mitochondria compared with WT or complex-I-deficient cells, suggesting that cells harboring defective OXPHOS trigger caspase-dependent as well as caspase-independent apoptosis in response to anticancer agents. Interestingly, DNA-damaging agent doxorubicin showed strong binding to mitochondria, which was disrupted by complex-I-deficiency but not by complex-II-deficiency. Thapsigargin-induced caspase activation was reduced upon abrogation of complex-I or gross OXPHOS deficiency whereas a reverse trend was observed with apicidin. Together, these finding provide a new strategy for differential mitochondrial targeting in cancer therapy.« less

Delivery of drugs, growth factors, genes and stem cells via intrapericardial, epicardial and intramyocardial routes for sustained local targeted therapy of myocardial disease.

PubMed

Maslov, Mikhail; Foianini, Stephan; Lovich, Mark

2017-10-01

Local myocardial delivery (LMD) of therapeutic agents is a promising strategy that aims to treat various myocardial pathologies. It is designed to deliver agents directly to the myocardium and minimize their extracardiac concentrations and side effects. LMD aims to enhance outcomes of existing therapies by broadening their therapeutic window and to utilize new agents that could not be otherwise be implemented systemically. Areas covered: This article provides a historical overview of six decades LMD evolution in terms of the approaches, including intrapericardial, epicardial, and intramyocardial delivery, and the wide array of classes of agents used to treat myocardial pathologies. We examines delivery of pharmaceutical compounds, targeted gene transfection and cell implantation techniques to produce therapeutic effects locally. We outline therapeutic indications, successes and failures as well as technical approaches for LMD. Expert opinion: While LMD is more complicated than conventional oral or intravenous administration, given recent advances in interventional cardiology, it is safe and may provide better therapeutic outcomes. LMD is complex as many factors impact pharmacokinetics and biologic result. The choice between routes of LMD is largely driven not only by the myocardial pathology but also by the nature and physicochemical properties of the therapeutic agents.

Membrane extraction with thermodynamically unstable diphosphonic acid derivatives

DOEpatents

Horwitz, E.P.; Gatrone, R.C.; Nash, K.L.

1997-10-14

Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulphur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described. 1 fig.

Extracting metal ions with diphosphonic acid, or derivative thereof

DOEpatents

Horwitz, Earl P.; Gatrone, Ralph C.; Nash, Kenneth L.

1994-01-01

Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulphur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described.

Extracting metal ions with diphosphonic acid, or derivative thereof

DOEpatents

Horwitz, E.P.; Gatrone, R.C.; Nash, K.L.

1994-07-26

Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulfur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described. 1 fig.

Self-assembly of PEGylated tetra-phenylalanine derivatives: structural insights from solution and solid state studies

PubMed Central

Diaferia, Carlo; Mercurio, Flavia Anna; Giannini, Cinzia; Sibillano, Teresa; Morelli, Giancarlo; Leone, Marilisa; Accardo, Antonella

2016-01-01

Water soluble fibers of PEGylated tetra-phenylalanine (F4), chemically modified at the N-terminus with the DOTA chelating agent, have been proposed as innovative contrast agent (CA) in Magnetic Resonance Imaging (MRI) upon complexation of the gadolinium ion. An in-depth structural characterization of PEGylated F4-fibers, in presence (DOTA-L6-F4) and in absence of DOTA (L6-F4), is reported in solution and at the solid state, by a multiplicity of techniques including CD, FTIR, NMR, DLS, WAXS and SAXS. This study aims to better understand how the aggregation process influences the performance of nanostructures as MRI CAs. Critical aggregation concentrations for L6-F4 (43 μM) and DOTA-L6-F4 (75 μM) indicate that self-aggregation process occurs in the same concentration range, independently of the presence of the CA. The driving force for the aggregation is the π-stacking between the side chains of the aromatic framework. CD, FTIR and WAXS measurements indicate an antiparallel β-sheet organization of the monomers in the resulting fibers. Moreover, WAXS and FTIR experiments point out that in solution the nanomaterials retain the same morphology and monomer organizations of the solid state, although the addition of the DOTA chelating agent affects the size and the degree of order of the fibers. PMID:27220817

Low temperature thermally regenerative electrochemical system

DOEpatents

Loutfy, Raouf O.; Brown, Alan P.; Yao, Neng-Ping

1983-01-01

A thermally regenerative electrochemical system including an electrochemical cell with two water-based electrolytes separated by an ion exchange membrane, at least one of the electrolytes containing a complexing agent and a salt of a multivalent metal whose respective order of potentials for a pair of its redox couples is reversible by a change in the amount of the complexing agent in the electrolyte, the complexing agent being removable by distillation to cause the reversal.

Emulating a System Dynamics Model with Agent-Based Models: A Methodological Case Study in Simulation of Diabetes Progression

DOE PAGES

Schryver, Jack; Nutaro, James; Shankar, Mallikarjun

2015-10-30

An agent-based simulation model hierarchy emulating disease states and behaviors critical to progression of diabetes type 2 was designed and implemented in the DEVS framework. The models are translations of basic elements of an established system dynamics model of diabetes. In this model hierarchy, which mimics diabetes progression over an aggregated U.S. population, was dis-aggregated and reconstructed bottom-up at the individual (agent) level. Four levels of model complexity were defined in order to systematically evaluate which parameters are needed to mimic outputs of the system dynamics model. Moreover, the four estimated models attempted to replicate stock counts representing disease statesmore » in the system dynamics model, while estimating impacts of an elderliness factor, obesity factor and health-related behavioral parameters. Health-related behavior was modeled as a simple realization of the Theory of Planned Behavior, a joint function of individual attitude and diffusion of social norms that spread over each agent s social network. Although the most complex agent-based simulation model contained 31 adjustable parameters, all models were considerably less complex than the system dynamics model which required numerous time series inputs to make its predictions. In all three elaborations of the baseline model provided significantly improved fits to the output of the system dynamics model. The performances of the baseline agent-based model and its extensions illustrate a promising approach to translate complex system dynamics models into agent-based model alternatives that are both conceptually simpler and capable of capturing main effects of complex local agent-agent interactions.« less

Emulating a System Dynamics Model with Agent-Based Models: A Methodological Case Study in Simulation of Diabetes Progression

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

Schryver, Jack; Nutaro, James; Shankar, Mallikarjun

An agent-based simulation model hierarchy emulating disease states and behaviors critical to progression of diabetes type 2 was designed and implemented in the DEVS framework. The models are translations of basic elements of an established system dynamics model of diabetes. In this model hierarchy, which mimics diabetes progression over an aggregated U.S. population, was dis-aggregated and reconstructed bottom-up at the individual (agent) level. Four levels of model complexity were defined in order to systematically evaluate which parameters are needed to mimic outputs of the system dynamics model. Moreover, the four estimated models attempted to replicate stock counts representing disease statesmore » in the system dynamics model, while estimating impacts of an elderliness factor, obesity factor and health-related behavioral parameters. Health-related behavior was modeled as a simple realization of the Theory of Planned Behavior, a joint function of individual attitude and diffusion of social norms that spread over each agent s social network. Although the most complex agent-based simulation model contained 31 adjustable parameters, all models were considerably less complex than the system dynamics model which required numerous time series inputs to make its predictions. In all three elaborations of the baseline model provided significantly improved fits to the output of the system dynamics model. The performances of the baseline agent-based model and its extensions illustrate a promising approach to translate complex system dynamics models into agent-based model alternatives that are both conceptually simpler and capable of capturing main effects of complex local agent-agent interactions.« less

Colorimetric detection of catalytic reactivity of nanoparticles in complex matrices.

PubMed

Corredor, Charlie; Borysiak, Mark D; Wolfer, Jay; Westerhoff, Paul; Posner, Jonathan D

2015-03-17

There is a need for new methodologies to quickly assess the presence and reactivity of nanoparticles (NPs) in commercial, environmental, and biological samples since current detection techniques require expensive and complex analytical instrumentation. Here, we investigate a simple and portable colorimetric detection assay that assesses the surface reactivity of NPs, which can be used to detect the presence of NPs, in complex matrices (e.g., environmental waters, serum, urine, and in dissolved organic matter) at as low as part per billion (ppb) or ng/mL concentration levels. Surface redox reactivity is a key emerging property related to potential toxicity of NPs with living cells, and is used in our assays as a key surrogate for the presence of NPs and a first tier analytical strategy toward assessing NP exposures. We detect a wide range of metal (e.g., Ag and Au) and oxide (e.g., CeO2, SiO2, VO2) NPs with a diameter range of 5 to 400 nm and multiple capping agents (tannic acid (TA), polyvinylpyrrolidone (PVP), branched polyethylenimine (BPEI), polyethylene glycol (PEG)). This method is sufficiently sensitive (ppb levels) to measure concentrations typically used in toxicological studies, and uses inexpensive, commercially available reagents.

Enhancement of sensitivity using hybrid stimulus for the diagnosis of prostate cancer based on polydiacetylene (PDA) supramolecules.

PubMed

Kwon, Il Kyoung; Kim, Jun Pyo; Sim, Sang Jun

2010-12-15

In this study, hybrid stimulus was initially introduced to improve the sensitivity of PDA vesicle chip for detection of prostate-specific antigen-α1-antichymotrypsin (PSA-ACT) complex. The strategy of hybrid stimulus on PDA vesicle chip offers the amplification method of fluorescent signal which combines a primary response by the immune reaction of antigen-antibody and a secondary response by the mechanical pressure of pAb-conjugated magnetic beads. As the primary response result on PDA vesicle chip, the PSA-ACT complex in PBS buffer was detected at 10 ng/mL. However, this detection sensitivity was insufficient for diagnosis of prostate cancer because the normal human PSA concentration is less than 4.0 ng/mL. To solve this problem, polyclonal PSA antibody-conjugated magnetic beads were used as an amplifying agent after primary immunoresponse. As a result, the PSA-ACT complex concentrations (as low as 0.1 ng/mL) could be detected in the PBS buffer sample. Therefore, this result can be applied to various fields, such as the detection of cells, proteins, and DNA for sensitive and specific biosensing based on PDA supramolecules. Copyright © 2010 Elsevier B.V. All rights reserved.

Unsilencing Critical Conversations in Social-Studies Teacher Education Using Agent-Based Modeling

ERIC Educational Resources Information Center

Hostetler, Andrew; Sengupta, Pratim; Hollett, Ty

2018-01-01

In this article, we argue that when complex sociopolitical issues such as ethnocentrism and racial segregation are represented as complex, emergent systems using agent-based computational models (in short agent-based models or ABMs), discourse about these representations can disrupt social studies teacher candidates' dispositions of teaching…

LED and low level laser therapy association in tooth bleaching using a novel low concentration H2O2/N-doped TiO2 bleaching agent

NASA Astrophysics Data System (ADS)

Bezerra Dias, Hércules; Teixeira Carrera, Emanuelle; Freitas Bortolatto, Janaína; Ferrarezi de Andrade, Marcelo; Nara de Souza Rastelli, Alessandra

2016-01-01

Since low concentration bleaching agents containing N-doped TiO2 nanoparticles have been introduced as an alternative to conventional agents, it is important to verify their efficacy and the hypersensitivity effect in clinical practice. Six volunteer patients were evaluated for color change and hypersensitivity after bleaching using 35% H2O2 (one session of two 12 min applications) and 6% H2O2/N-doped TiO2 (one session of three 12 min applications) and after low level laser therapy application (LLLT) (780 nm, 40 mW, 10 J.cm-2, 10 s). Based on this case study, the nanobleaching agent provided better or similar aesthetic results than the conventional agent under high concentration, and its association with LLLT satisfactorily decreased the hypersensitivity. The 6% H2O2/N-doped TiO2 agent could be used instead of conventional in-office bleaching agents under high concentrations to fulfill the rising patient demand for aesthetics.

Cu2ZnSnS4 Nanoparticles Synthesized by a Novel Diethylenetriamine-Assisted Hydrothermal Method

NASA Astrophysics Data System (ADS)

Liang, Feng; Gao, Juan; Zou, Changwei; Shao, Lexi

2018-05-01

A diethylenetriamine (DETA)-assisted hydrothermal method was explored for the synthesis of kesterite Cu2ZnSnS4 (CZTS) nanoparticles. As complexing agent, DETA was employed to dissolve sulfur and to form complex with metal ions. By introducing DETA to the system, pure CZTS nanoparticles with bandgap of 1.54 eV could be successfully obtained and the agglomeration of samples could be restrained by increasing the concentration of DETA. From the discussion about the experimental results, the formation mechanism of CZTS nanoparticles was proposed. As the reagents used in this experiment is low-toxic and inexpensive, this method was considered as an effective and green route for the synthesis of CZTS nanoparticles.

Intelligent Agent Architectures: Reactive Planning Testbed

NASA Technical Reports Server (NTRS)

Rosenschein, Stanley J.; Kahn, Philip

1993-01-01

An Integrated Agent Architecture (IAA) is a framework or paradigm for constructing intelligent agents. Intelligent agents are collections of sensors, computers, and effectors that interact with their environments in real time in goal-directed ways. Because of the complexity involved in designing intelligent agents, it has been found useful to approach the construction of agents with some organizing principle, theory, or paradigm that gives shape to the agent's components and structures their relationships. Given the wide variety of approaches being taken in the field, the question naturally arises: Is there a way to compare and evaluate these approaches? The purpose of the present work is to develop common benchmark tasks and evaluation metrics to which intelligent agents, including complex robotic agents, constructed using various architectural approaches can be subjected.

Metal complexes of curcumin for cellular imaging, targeting, and photoinduced anticancer activity.

PubMed

Banerjee, Samya; Chakravarty, Akhil R

2015-07-21

Curcumin is a polyphenolic species. As an active ingredient of turmeric, it is well-known for its traditional medicinal properties. The therapeutic values include antioxidant, anti-inflammatory, antiseptic, and anticancer activity with the last being primarily due to inhibition of the transcription factor NF-κB besides affecting several biological pathways to arrest tumor growth and its progression. Curcumin with all these positive qualities has only remained a potential candidate for cancer treatment over the years without seeing any proper usage because of its hydrolytic instability involving the diketo moiety in a cellular medium and its poor bioavailability. The situation has changed considerably in recent years with the observation that curcumin in monoanionic form could be stabilized on binding to a metal ion. The reports from our group and other groups have shown that curcumin in the metal-bound form retains its therapeutic potential. This has opened up new avenues to develop curcumin-based metal complexes as anticancer agents. Zinc(II) complexes of curcumin are shown to be stable in a cellular medium. They display moderate cytotoxicity against prostate cancer and neuroblastoma cell lines. A similar stabilization and cytotoxic effect is reported for (arene)ruthenium(II) complexes of curcumin against a variety of cell lines. The half-sandwich 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane (RAPTA)-type ruthenium(II) complexes of curcumin are shown to be promising cytotoxic agents with low micromolar concentrations for a series of cancer cell lines. In a different approach, cobalt(III) complexes of curcumin are used for its cellular delivery in hypoxic tumor cells using intracellular agents that reduce the metal and release curcumin as a cytotoxin. Utilizing the photophysical and photochemical properties of the curcumin dye, we have designed and synthesized photoactive curcumin metal complexes that are used for cellular imaging by fluorescence microscopy and damaging the cancer cells on photoactivation in visible light while being minimally toxic in darkness. In this Account, we have made an attempt to review the current status of the chemistry of metal curcumin complexes and present results from our recent studies on curcumin complexes showing remarkable in vitro photocytotoxicity. The undesirable dark toxicity of the complexes can be reduced with suitable choice of the metal and the ancillary ligands in a ternary structure. The complexes can be directed to specific subcellular organelles. Selectivity by targeting cancer cells over normal cells can be achieved with suitable ligand design. We expect that this methodology is likely to provide an impetus toward developing curcumin-based photochemotherapeutics for anticancer treatment and cure.

Antitumor activity of resveratrol is independent of Cu(II) complex formation in MCF-7 cell line.

PubMed

Andrade Volkart, Priscylla; Benedetti Gassen, Rodrigo; Mühlen Nogueira, Bettina; Nery Porto, Bárbara; Eduardo Vargas, José; Arigony Souto, André

2017-08-01

Resveratrol (Rsv) is widely reported to possess anticarcinogenic properties in a plethora of cellular and animal models having limited toxicity toward normal cells. In the molecular level, Rsv can act as a suppressive agent for several impaired signaling pathways on cancer cells. However, Fukuhara and Miyata have shown a non-proteic reaction of Rsv, which can act as a prooxidant agent in the presence of copper (Cu), causing cellular oxidative stress accompanied of DNA damage. After this discovery, the complex Rsv-Cu was broadly explored as an antitumor mechanism in multiples tumor cell lines. The aim of the study is to explore the anticarcinogenic behavior of resveratrol-Cu(II) complex in MCF-7 cell line. Selectivity of Rsv binding to Cu ions was analyzed by HPLC and UV-VIS. The cells were enriched with concentrations of 10 and 50µM CuSO 4 solution and treated with 25µM of Rsv. Copper uptake after enrichment of cells, as its intracellular distribution in MCF-7 line, was scanned by ICP-MS and TEM-EDS. Cell death and intracellular ROS production were determined by flow cytometry. Different from the extracellular model, no relationship of synergy between Rsv-Cu(II) and reactive oxidative species (ROS) production was detected in vitro. ICP-MS revealed intracellular copper accumulation to both chosen concentrations (0.33±0.09 and 1.18±0.13ppb) but there is no promotion of cell death by Rsv-Cu(II) complex. In addition, significant attenuation of ROS production was detected when cells were exposed to CuSO 4 after Rsv treatment, falling from 7.54% of ROS production when treated only with Rsv to 3.07 and 2.72% with CuSO 4 . Based on these findings antitumor activity of resveratrol when in copper ions presence, is not mediated by Rsv-Cu complex formation in MCF-7 human cell line, suggesting that the antitumoral reaction is dependent of a cancer cellular model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Handheld Delivery System for Modified Boron-Type Fire Extinguishment Agent

DTIC Science & Technology

1993-11-01

was to develop and test a handheld portable delivery system for use with the modified boron-type fire extinguishing agent for metal fires . B...BACKGROUND A need exists for an extinguishing agent and accompanying delivery system that are effective against complex geometry metal fires . A modified...agent and its delivery system have proven effective against complex geometry metal fires containing up to 200 pounds of magnesium metal. Further

Constants for mercury binding by organic matter isolates from the Florida Everglades

USGS Publications Warehouse

Benoit, J.M.; Mason, R.P.; Gilmour, C.C.; Aiken, G.R.

2001-01-01

Dissolved organic matter (DOM) has been implicated as an important complexing agent for Hg that can affect its mobility and bioavailability in aquatic ecosystems. However, binding constants for natural Hg-DOM complexes are not well known. We employed a competitive ligand approach to estimate conditional stability constants for Hg complexes with DOM isolates collected from Florida Everglades surface waters. The isolates examined were the hydrophobic fraction of DOM from a eutrophic, sulfidic site (F1-HPoA) and the hydrophilic fraction from an oligotrophic, low-sulfide site (2BS-HPiA). Our experimental determinations utilized overall octanol-water partitioning coefficients (Dow) for 203Hg at 0.01 M chloride and across pH and DOM concentration gradients. Use of this radioisotope allowed rapid determinations of Hg concentrations in both water and octanol phases without problems of matrix interference. Conditional stability constants (1 = 0.06, 23??C) were log K??? = 11.8 for F1-HPoA and log K' = 10.6 for 2BS-HPiA. These are similar to previously published stability constants for Hg binding to low-molecular-weight thiols. Further, F1-HPoA showed a pH-dependent decline in Dow that was consistent with models of Hg complexation with thiol groups as the dominant Hg binding sites in DOM. These experiments demonstrate that the DOM isolates are stronger ligands for Hg than chloride ion or ethylenediamine-tetraacetic acid. Speciation calculations indicate that at the DOM concentrations frequently measured in Everglades, 20 to 40 ??M, significant complexation of Hg by DOM would be expected in aerobic (sulfide-free) surface waters. Copyright ?? 2001 Elsevier Science Ltd.

In vitro evaluation of the cyto-genotoxic potential of Ruthenium(II) SCAR complexes: a promising class of antituberculosis agents.

PubMed

De Grandis, Rone Aparecido; Resende, Flávia Aparecida; da Silva, Monize Martins; Pavan, Fernando Rogério; Batista, Alzir Azevedo; Varanda, Eliana Aparecida

2016-03-01

Tuberculosis is a top infectious disease killer worldwide, caused by the bacteria Mycobacterium tuberculosis. Increasing incidences of multiple drug-resistance (MDR) strains are emerging as one of the major public health threats. However, the drugs in use are still incapable of controlling the appalling upsurge of MDR. In recent years a marked number of research groups have devoted their attention toward the development of specific and cost-effective antimicrobial agents against targeted MDR-Tuberculosis. In previous studies, ruthenium(II) complexes (SCAR) have shown a promising activity against MDR-Tuberculosis although few studies have indeed considered ruthenium toxicity. Therefore, within the preclinical requirements, we have sought to determine the cyto-genotoxicity of three SCAR complexes in this present study. The treatment with the SCARs induced a concentration-dependent decrease in cell viability in CHO-K1 and HepG2 cells. Based on the clonogenic survival, SCAR 5 was found to be more cytotoxic while SCAR 6 exhibited selectivity action on tumor cells. Although SCAR 4 and 5 did not indicate any mutagenic activity as evidenced by the Ames and Cytokinesis block micronucleus cytome assays, the complex SCAR 6 was found to engender a frameshift mutation detected by Salmonella typhimurium in the presence of S9. Similarly, we observed a chromosomal damage in HepG2 cells with significant increases of micronuclei and nucleoplasmic bridges. These data indicate that SCAR 4 and 5 complexes did not show genotoxicity in our models while SCAR 6 was considered mutagenic. This study presented a comprehensive genotoxic evaluation of SCAR complexes were shown to be genotoxic in vitro. All in all, further studies are required to fully elucidate how the properties can affect human health. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel metals and metal complexes as platforms for cancer therapy.

PubMed

Frezza, Michael; Hindo, Sarmad; Chen, Di; Davenport, Andrew; Schmitt, Sara; Tomco, Dajena; Dou, Q Ping

2010-06-01

Metals are essential cellular components selected by nature to function in several indispensable biochemical processes for living organisms. Metals are endowed with unique characteristics that include redox activity, variable coordination modes, and reactivity towards organic substrates. Due to their reactivity, metals are tightly regulated under normal conditions and aberrant metal ion concentrations are associated with various pathological disorders, including cancer. For these reasons, coordination complexes, either as drugs or prodrugs, become very attractive probes as potential anticancer agents. The use of metals and their salts for medicinal purposes, from iatrochemistry to modern day, has been present throughout human history. The discovery of cisplatin, cis-[Pt(II) (NH(3))(2)Cl(2)], was a defining moment which triggered the interest in platinum(II)- and other metal-containing complexes as potential novel anticancer drugs. Other interests in this field address concerns for uptake, toxicity, and resistance to metallodrugs. This review article highlights selected metals that have gained considerable interest in both the development and the treatment of cancer. For example, copper is enriched in various human cancer tissues and is a co-factor essential for tumor angiogenesis processes. However the use of copper-binding ligands to target tumor copper could provide a novel strategy for cancer selective treatment. The use of nonessential metals as probes to target molecular pathways as anticancer agents is also emphasized. Finally, based on the interface between molecular biology and bioinorganic chemistry the design of coordination complexes for cancer treatment is reviewed and design strategies and mechanisms of action are discussed.

In vitro inhibition of hyaluronidase by sodium copper chlorophyllin complex and chlorophyllin analogs

PubMed Central

McCook, John P; Dorogi, Peter L; Vasily, David B; Cefalo, Dustin R

2015-01-01

Background Inhibitors of hyaluronidase are potent agents that maintain hyaluronic acid homeostasis and may serve as anti-aging, anti-inflammatory, and anti-microbial agents. Sodium copper chlorophyllin complex is being used therapeutically as a component in anti-aging cosmeceuticals, and has been shown to have anti-hyaluronidase activity. In this study we evaluated various commercial lots of sodium copper chlorophyllin complex to identify the primary small molecule constituents, and to test various sodium copper chlorophyllin complexes and their small molecule analog compounds for hyaluronidase inhibitory activity in vitro. Ascorbate analogs were tested in combination with copper chlorophyllin complexes for potential additive or synergistic activity. Materials and methods For hyaluronidase activity assays, dilutions of test materials were evaluated for hydrolytic activity of hyaluronidase by precipitation of non-digested hyaluronate by measuring related turbidity at 595 nm. High-performance liquid chromatography and mass spectroscopy was used to analyze and identify the primary small molecule constituents in various old and new commercial lots of sodium copper chlorophyllin complex. Results The most active small molecule component of sodium copper chlorophyllin complex was disodium copper isochlorin e4, followed by oxidized disodium copper isochlorin e4. Sodium copper chlorophyllin complex and copper isochlorin e4 disodium salt had hyaluronidase inhibitory activity down to 10 µg/mL. The oxidized form of copper isochlorin e4 disodium salt had substantial hyaluronidase inhibitory activity at 100 µg/mL but not at 10 µg/mL. Ascorbate derivatives did not enhance the hyaluronidase inhibitory activity of sodium copper chlorophyllin. Copper isochlorin e4 analogs were always the dominant components of the small molecule content of the commercial lots tested; oxidized copper isochlorin e4 was found in increased concentrations in older compared to newer lots tested. Conclusion These results support the concept of using the hyaluronidase inhibitory activity of sodium copper chlorophyllin complex to increase the hyaluronic acid level of the dermal extracellular matrix for the improvement of the appearance of aging facial skin. PMID:26300653

In vitro inhibition of hyaluronidase by sodium copper chlorophyllin complex and chlorophyllin analogs.

PubMed

McCook, John P; Dorogi, Peter L; Vasily, David B; Cefalo, Dustin R

2015-01-01

Inhibitors of hyaluronidase are potent agents that maintain hyaluronic acid homeostasis and may serve as anti-aging, anti-inflammatory, and anti-microbial agents. Sodium copper chlorophyllin complex is being used therapeutically as a component in anti-aging cosmeceuticals, and has been shown to have anti-hyaluronidase activity. In this study we evaluated various commercial lots of sodium copper chlorophyllin complex to identify the primary small molecule constituents, and to test various sodium copper chlorophyllin complexes and their small molecule analog compounds for hyaluronidase inhibitory activity in vitro. Ascorbate analogs were tested in combination with copper chlorophyllin complexes for potential additive or synergistic activity. For hyaluronidase activity assays, dilutions of test materials were evaluated for hydrolytic activity of hyaluronidase by precipitation of non-digested hyaluronate by measuring related turbidity at 595 nm. High-performance liquid chromatography and mass spectroscopy was used to analyze and identify the primary small molecule constituents in various old and new commercial lots of sodium copper chlorophyllin complex. The most active small molecule component of sodium copper chlorophyllin complex was disodium copper isochlorin e4, followed by oxidized disodium copper isochlorin e4. Sodium copper chlorophyllin complex and copper isochlorin e4 disodium salt had hyaluronidase inhibitory activity down to 10 µg/mL. The oxidized form of copper isochlorin e4 disodium salt had substantial hyaluronidase inhibitory activity at 100 µg/mL but not at 10 µg/mL. Ascorbate derivatives did not enhance the hyaluronidase inhibitory activity of sodium copper chlorophyllin. Copper isochlorin e4 analogs were always the dominant components of the small molecule content of the commercial lots tested; oxidized copper isochlorin e4 was found in increased concentrations in older compared to newer lots tested. These results support the concept of using the hyaluronidase inhibitory activity of sodium copper chlorophyllin complex to increase the hyaluronic acid level of the dermal extracellular matrix for the improvement of the appearance of aging facial skin.

[Comparative efficiency of nootropic drugs in complex treatment of patients with remote consequences of closed craniocereberal trauma].

PubMed

Hliebova, O S; Tkachenko, O V

2008-01-01

Main data of the research were data obtained after a complex treatment of 120 persons with late consequences of closed craniocereberal trauma (CCRCT). The treatment included administration of one of nootropic agents (noophen, aminolon or entropil), magnesium sulfate, group B vitamins. All patients have passed a complex examination: specially developed questionnaire, anamnesis gathering, neurologic status, neuropsychological status with the use of multiple-aspect scales and questionnaires, examination of fundus of eye, rheoencephalography, echoencephalography, brain MRT. Results of a complex examination proved positive effect of the use of nootropic agents, in particular noophen, entropil and aminolon in complex treatment of late consequences of closed craniocereberal trauma. For optimisation of the use of nootropic agents in the treatment of late consequences of closed craniocereberal trauma it is recommended to consider features of influence of nootropic agents on certain clinical aspects of the disease.

Conformational changes induced in the eukaryotic translation initiation factor eIF4E by a clinically relevant inhibitor, ribavirin triphosphate

PubMed Central

Volpon, Laurent; Osborne, Michael J.; Zahreddine, Hiba; Romeo, Andrea A.; Borden, Katherine L.B.

2013-01-01

The eukaryotic translation initiation factor eIF4E is highly elevated in human cancers including acute myeloid leukemia (AML). A potential anticancer agent, ribavirin, targets eIF4E activity in AML patients corresponding to clinical responses. To date, ribavirin is the only direct inhibitor of eIF4E to reach clinical trials. We showed that ribavirin acts as a competitive inhibitor of the methyl 7-guanosine (m7G) cap, the natural ligand of eIF4E. Here we examine the conformational changes occurring in human eIF4E upon binding the active metabolite of ribavirin, ribavirin triphosphate (RTP). Our NMR data revealed an unexpected concentration dependence on RTP affinity for eIF4E. We observed NMR spectra characteristic of tight binding at low micromolar concentrations (2-5μM eIF4E) but much weaker affinity at more typical NMR concentrations (50-200μM). Comparison of chemical shift perturbation and line broadening suggest that the two eIF4E-RTP complexes differ in the precise positioning of RTP within the cap binding pocket, with the high affinity complex showing more extensive changes to the central β-sheet and dorsal surface of eIF4E, similar to m7G cap. The differences between high and low affinity complexes arise due to concentration dependent aggregation of eIF4E and RTP. Given the intracellular concentrations of eIF4E and RTP and the differential binding toward the W56A eIF4E mutant the high affinity complex is the most physiologically relevant. In summary, these findings demonstrate that RTP binds in the cap-binding site but also suggests new features of this pocket that should be considered in both drug design efforts and reveal new insights into ligand eIF4E recognition. PMID:23583375

Modeling the Internet of Things, Self-Organizing and Other Complex Adaptive Communication Networks: A Cognitive Agent-Based Computing Approach

PubMed Central

2016-01-01

Background Computer Networks have a tendency to grow at an unprecedented scale. Modern networks involve not only computers but also a wide variety of other interconnected devices ranging from mobile phones to other household items fitted with sensors. This vision of the "Internet of Things" (IoT) implies an inherent difficulty in modeling problems. Purpose It is practically impossible to implement and test all scenarios for large-scale and complex adaptive communication networks as part of Complex Adaptive Communication Networks and Environments (CACOONS). The goal of this study is to explore the use of Agent-based Modeling as part of the Cognitive Agent-based Computing (CABC) framework to model a Complex communication network problem. Method We use Exploratory Agent-based Modeling (EABM), as part of the CABC framework, to develop an autonomous multi-agent architecture for managing carbon footprint in a corporate network. To evaluate the application of complexity in practical scenarios, we have also introduced a company-defined computer usage policy. Results The conducted experiments demonstrated two important results: Primarily CABC-based modeling approach such as using Agent-based Modeling can be an effective approach to modeling complex problems in the domain of IoT. Secondly, the specific problem of managing the Carbon footprint can be solved using a multiagent system approach. PMID:26812235

Effect of complexing agents on the electrochemical performance of LiFePO4/C prepared by sol-gel method

PubMed Central

2012-01-01

LiFePO4/C is synthesized via sol-gel method using Fe3+ as iron sources and different complexing agents, followed by sintering at high temperature for crystallization. The amount of carbon in these composites is less than 6.8 wt.%, and the X-ray diffraction experiment confirms that all samples are pure single phase indexed with the orthorhombic Pnma space group. The particle size of the LiFePO4/C synthesized by acetic acid as a complexing agent is very fine with a size of 200 nm. The electrochemical performance of this material, including reversible capacity, cycle number, and charge-discharge characteristics, is better than those of LiFePO4/C synthesized by other complexing agents. The cell of this sample can deliver a discharge capacity of 161.1 mAh g-1 at the first cycle. After 30 cycles, the capacity decreases to 157.5 mAh g-1, and the capacity fading rate is 2.2%. The mechanism is studied to explain the effect of a complexing agent on the synthesis of LiFePO4/C by sol-gel method. The results show that the complexing agent with a low stability constant may be proper for the synthetic process of LiFePO4/C via sol-gel method. PMID:22221711

Effect of complexing agents on the electrochemical performance of LiFePO4/C prepared by sol-gel method

NASA Astrophysics Data System (ADS)

Yang, Rong; Kang, Erwei; Jiang, Bailing; Ahn, Jou-Hyeon

2012-01-01

LiFePO4/C is synthesized via sol-gel method using Fe3+ as iron sources and different complexing agents, followed by sintering at high temperature for crystallization. The amount of carbon in these composites is less than 6.8 wt.%, and the X-ray diffraction experiment confirms that all samples are pure single phase indexed with the orthorhombic Pnma space group. The particle size of the LiFePO4/C synthesized by acetic acid as a complexing agent is very fine with a size of 200 nm. The electrochemical performance of this material, including reversible capacity, cycle number, and charge-discharge characteristics, is better than those of LiFePO4/C synthesized by other complexing agents. The cell of this sample can deliver a discharge capacity of 161.1 mAh g-1 at the first cycle. After 30 cycles, the capacity decreases to 157.5 mAh g-1, and the capacity fading rate is 2.2%. The mechanism is studied to explain the effect of a complexing agent on the synthesis of LiFePO4/C by sol-gel method. The results show that the complexing agent with a low stability constant may be proper for the synthetic process of LiFePO4/C via sol-gel method.

Toxicity bioassays with concentrated cell culture media-a methodology to overcome the chemical loss by conventional preparation of water samples.

PubMed

Niss, Frida; Rosenmai, Anna Kjerstine; Mandava, Geeta; Örn, Stefan; Oskarsson, Agneta; Lundqvist, Johan

2018-04-01

The use of in vitro bioassays for studies of toxic activity in environmental water samples is a rapidly expanding field of research. Cell-based bioassays can assess the total toxicity exerted by a water sample, regardless whether the toxicity is caused by a known or unknown agent or by a complex mixture of different agents. When using bioassays for environmental water samples, it is often necessary to concentrate the water samples before applying the sample. Commonly, water samples are concentrated 10-50 times. However, there is always a risk of losing compounds in the sample in such sample preparation. We have developed an alternative experimental design by preparing a concentrated cell culture medium which was then diluted in the environmental water sample to compose the final cell culture media for the in vitro assays. Water samples from five Swedish waste water treatment plants were analyzed for oxidative stress response, estrogen receptor (ER), and aryl hydrocarbon receptor (AhR) activity using this experimental design. We were able to detect responses equivalent to 8.8-11.3 ng/L TCCD for AhR activity and 0.4-0.9 ng/L 17β-estradiol for ER activity. We were unable to detect oxidative stress response in any of the studied water samples. In conclusion, we have developed an experimental design allowing us to examine environmental water samples in toxicity in vitro assays at a concentration factor close to 1, without the risk of losing known or unknown compounds during an extraction procedure.

Formalizing the Role of Agent-Based Modeling in Causal Inference and Epidemiology

PubMed Central

Marshall, Brandon D. L.; Galea, Sandro

2015-01-01

Calls for the adoption of complex systems approaches, including agent-based modeling, in the field of epidemiology have largely centered on the potential for such methods to examine complex disease etiologies, which are characterized by feedback behavior, interference, threshold dynamics, and multiple interacting causal effects. However, considerable theoretical and practical issues impede the capacity of agent-based methods to examine and evaluate causal effects and thus illuminate new areas for intervention. We build on this work by describing how agent-based models can be used to simulate counterfactual outcomes in the presence of complexity. We show that these models are of particular utility when the hypothesized causal mechanisms exhibit a high degree of interdependence between multiple causal effects and when interference (i.e., one person's exposure affects the outcome of others) is present and of intrinsic scientific interest. Although not without challenges, agent-based modeling (and complex systems methods broadly) represent a promising novel approach to identify and evaluate complex causal effects, and they are thus well suited to complement other modern epidemiologic methods of etiologic inquiry. PMID:25480821

Effects of complexing agents on electrochemical deposition of FeS x O y in ZnO/FeS x O y heterostructures

NASA Astrophysics Data System (ADS)

Supee, A.; Ichimura, M.

2017-12-01

Heterostructures which consist of ZnO and FeS x O y were deposited via electrochemical deposition (ECD) for application to solar cells. Galvanostatic ECD was used in FeS x O y deposition with a solution containing 100 mM Na2S2O3 and 30 mM FeSO4. To alter the film properties, L(+)-tartaric acid (C4H6O6) and lactic acid [CH3CH(OH)COOH] were introduced as the complexing agents into the FeS x O y deposition solution. Larger film thickness and smaller oxygen content were obtained for the films deposited with the complexing agents. ZnO was deposited on FeS x O y by two-step pulse ECD from a solution containing Zn(NO3)2. For the ZnO/FeS x O y heterostructures fabricated with/without complexing agents, rectifying properties were confirmed in the current density-voltage ( J- V) characteristics. However, photovoltaic properties were not improved with addition of both complexing agents.

A novel method of reducing agent contacting pattern for metal ceramic composite membrane fabrication

NASA Astrophysics Data System (ADS)

Agarwal, Amrita; Pujari, Murali; Uppaluri, Ramgopal; Verma, Anil

2014-11-01

Deliberating upon process modifications for surfactant induced electroless plating (SIEP), this article highlights the plating bath performance characteristics for two distinct reducing agent contacting modes (bulk and drop wise). Eventually, the effect of reducing agent concentration (50, 100, 200% excess) suitable for electroless plating bath for a nickel concentration of 0.08 mol/L was investigated. Finally, the compatibility of variation in nickel concentration (0.08-0.24 mol/L) with respect to variation in reducing agent concentration (50, 100, 200% excess) was investigated. LPSA, BET, FTIR, XRD, FESEM and nitrogen permeation experiments were used for surface and physical characterization. It was observed that for the bulk addition of reducing agent, the PPD values were 84.5% which increased to 89.3% for dropwise addition case. Thus the optimal combinations of SIEP process parameters were identified as 0.08 mol/L of nickel metal solution concentration with 100% excess drop-wise reducing agent. These conditions provided a plating rate of 5.5 × 10-5 mol/m2 s, PPD of 89.3% and a metal film thickness of 15.7 μm respectively after 12 h of sequential plating.

Vapor Pressures of Anesthetic Agents at Temperatures below Zero Degrees Celsius and a Novel Anesthetic Delivery Device

PubMed Central

Schenning, Katie J.; Casson, Henry; Click, Sarah V.; Brambrink, Lucas; Chatkupt, Thomas T.; Alkayed, Nabil J.; Hutchens, Michael P.

2016-01-01

At room temperature, the vapor pressures of desflurane, isoflurane, and sevoflurane are well above the clinically useful range. We hypothesized that therapeutic concentrations of these agents could be achieved at temperatures below zero, but the vapor pressure-temperature relationship is unknown below zero. Secondarily, we hypothesized that this relationship could be exploited to deliver therapeutic-range concentrations of anesthetic vapor. We therefore set out to determine the low temperature-vapor pressure relationships of each anesthetic agent thereby identifying the saturated vapor concentration of each agent at any temperature below zero. To test our hypothesis, we measured the saturated vapor concentration at 1 atmosphere of pressure for temperatures between -60°C and 0°C thus developing an empiric relationship for each agent. There was consistency in repeated experiments for all three agents. To test the empiric data we constructed a digitally-controlled thermoelectric anesthetic vaporizer, characterized the device, and used it to deliver anesthetic vapor to laboratory mice. We report, for the first time, the temperature-vapor pressure relationship at temperatures below 0°C for desflurane, isoflurane, and sevoflurane as well as the TMAC of these agents: the temperature at which the vapor pressure is equal to the minimum alveolar concentration. We describe the construction and limited validation of an anesthetic vaporizer prototype based on this principle. We conclude that clinically relevant concentrations of volatile anesthetics may be achieved at low temperatures. PMID:27632346

Vapor Pressures of Anesthetic Agents at Temperatures Below 0°C and a Novel Anesthetic Delivery Device.

PubMed

Schenning, Katie J; Casson, Henry; Click, Sarah V; Brambrink, Lucas; Chatkupt, Thomas T; Alkayed, Nabil J; Hutchens, Michael P

2017-02-01

At room temperature, the vapor pressures of desflurane, isoflurane, and sevoflurane are well above the clinically useful range. We hypothesized that therapeutic concentrations of these agents could be achieved at temperatures below 0°C, but the vapor pressure-temperature relationship is unknown below 0. Second, we hypothesized that this relationship could be exploited to deliver therapeutic-range concentrations of anesthetic vapor. We therefore set out to determine the low temperature-vapor pressure relationships of each anesthetic agent, thereby identifying the saturated vapor concentration of each agent at any temperature below 0°C. To test our hypothesis, we measured the saturated vapor concentration at 1 atm of pressure for temperatures between -60 and 0°C, thus developing an empiric relationship for each agent. There was consistency in repeated experiments for all 3 agents. To test the empiric data, we constructed a digitally controlled thermoelectric anesthetic vaporizer, characterized the device, and used it to deliver anesthetic vapor to laboratory mice. We report, for the first time, the temperature-vapor pressure relationship at temperatures below 0°C for desflurane, isoflurane, and sevoflurane as well as the TMAC of these agents: the temperature at which the vapor pressure is equal to the minimum alveolar concentration. We describe the construction and limited validation of an anesthetic vaporizer prototype on the basis of this principle. We conclude that clinically relevant concentrations of volatile anesthetics may be achieved at low temperatures.

Effect of clavulanic acid on minimal inhibitory concentrations of 16 antimicrobial agents tested against Legionella pneumophila.

PubMed Central

Pohlod, D J; Saravolatz, L D; Quinn, E L; Somerville, M M

1980-01-01

A total of 15 Legionella pneumophilia isolated were tested against 16 antimicrobial agents used singly and in combination with clavulanic acid. When combined with clavulanic acid, 4 of the 16 antimicrobial agents produced no enhanced effect. However, the minimal inhibitory concentrations of 12 of the antimicrobial agents were reduced by one-half to one-third when in combination with clavulanic acid. These reductions reflected only a one-dilution decrease, however, in the original minimal inhibitory concentrations. Thus, clavulanic acid combinations appear to be only nominally effective beta-lactamase inhibitors against L. pneumophilia. PMID:6969575

Synthesis and spectroscopic studies of Ru(II) complexes of steroidal thiosemicarbazones by multi step reaction: As anti-bacterial agents.

PubMed

Khan, Salman A; Asiri, Abdullah M

2017-08-01

Ru(II) steroidal metal complexes were synthesized by the reaction of dichlorodicarbonyl ruthenium(II) [Ru(CO) 2 Cl 2 ] n with Steroidal thiosemicarbazones. Coordination via the thionic sulfur and the azomethine nitrogen atom of the thiosemicarbazone to the Ru(II) metal. Steroidal thiosemicarbazone derivatives were obtained by the thiosemicarbazide with steroidal ketones. Structures of the steroidal thiosemicarbazone and their metal complexes were confirmed by the FT-IR, 1 H NMR, 13 C NMR, Fab-Mass spectroscopy and elemental analysis. The antibacterial activity of these compounds were first tested in vitro by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) was determined. The results showed that steroidal Ru(II) complexes are better inhibit growth as compared to steroidal thiosemicarbazones of both types of the bacteria (gram-positive and gram-negative). Copyright © 2017 Elsevier Inc. All rights reserved.

Distributed Cooperation Solution Method of Complex System Based on MAS

NASA Astrophysics Data System (ADS)

Weijin, Jiang; Yuhui, Xu

To adapt the model in reconfiguring fault diagnosing to dynamic environment and the needs of solving the tasks of complex system fully, the paper introduced multi-Agent and related technology to the complicated fault diagnosis, an integrated intelligent control system is studied in this paper. Based on the thought of the structure of diagnostic decision and hierarchy in modeling, based on multi-layer decomposition strategy of diagnosis task, a multi-agent synchronous diagnosis federation integrated different knowledge expression modes and inference mechanisms are presented, the functions of management agent, diagnosis agent and decision agent are analyzed, the organization and evolution of agents in the system are proposed, and the corresponding conflict resolution algorithm in given, Layered structure of abstract agent with public attributes is build. System architecture is realized based on MAS distributed layered blackboard. The real world application shows that the proposed control structure successfully solves the fault diagnose problem of the complex plant, and the special advantage in the distributed domain.

Use of Artificial Neural Networks to Examine Parameters Affecting the Immobilization of Streptokinase in Chitosan

PubMed Central

Modaresi, Seyed Mohamad Sadegh; Faramarzi, Mohammad Ali; Soltani, Arash; Baharifar, Hadi; Amani, Amir

2014-01-01

Streptokinase is a potent fibrinolytic agent which is widely used in treatment of deep vein thrombosis (DVT), pulmonary embolism (PE) and acute myocardial infarction (MI). Major limitation of this enzyme is its short biological half-life in the blood stream. Our previous report showed that complexing streptokinase with chitosan could be a solution to overcome this limitation. The aim of this research was to establish an artificial neural networks (ANNs) model for identifying main factors influencing the loading efficiency of streptokinase, as an essential parameter determining efficacy of the enzyme. Three variables, namely, chitosan concentration, buffer pH and enzyme concentration were considered as input values and the loading efficiency was used as output. Subsequently, the experimental data were modeled and the model was validated against a set of unseen data. The developed model indicated chitosan concentration as probably the most important factor, having reverse effect on the loading efficiency. PMID:25587327

Reversal of apixaban anticoagulation by four-factor prothrombin complex concentrates in healthy subjects: a randomized three-period crossover study.

PubMed

Song, Y; Wang, Z; Perlstein, I; Wang, J; LaCreta, F; Frost, R J A; Frost, C

2017-11-01

Essentials Prothrombin complex concentrates (PCCs) may reverse the effect of factor Xa (FXa) inhibitors. We conducted an open-label, randomized, placebo-controlled, three-period crossover study in 15 subjects. Both PCCs rapidly reversed apixaban-mediated decreases in mean endogenous thrombin potential. Four-factor PCC administration had no effect on apixaban pharmacokinetics or anti-FXa activity. Background Currently, there is no approved reversal agent for direct activated factor Xa (FXa) inhibitors; however, several agents are under investigation, including prothrombin complex concentrates (PCCs). Objective This open-label, randomized, placebo-controlled, three-period crossover study assessed the effect of two four-factor PCCs on apixaban pharmacodynamics and pharmacokinetics in 15 healthy subjects. Methods Subjects received apixaban 10 mg twice daily for 3 days. On day 4, 3 h after apixaban, subjects received a 30-min infusion of 50 IU kg -1 Cofact, Beriplex P/N (Beriplex), or saline. Change in endogenous thrombin potential (ETP), measured with a thrombin generation assay (TGA), was the primary endpoint. Secondary endpoints included changes in other TGA parameters, prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time, anti-FXa activity, apixaban pharmacokinetics, and safety. Results Apixaban-related changes in ETP and several other pharmacodynamic measures occurred following apixaban administration. Both PCCs reversed apixaban's effect on ETP; the differences in adjusted mean change from pre-PCC baseline to end of infusion were 425 nm min (95% confidence interval [CI] 219.8-630.7 nm min; P < 0.001) for Cofact, and 91 nm min (95% CI - 31.3 to 212.4 nm min; P > 0.05) for Beriplex. Both PCCs returned ETP to pre-apixaban baseline levels 4 h after PCC infusion, versus 45 h for placebo. For both PCCs, mean ETP peaked 21 h after PCC initiation, and then slowly decreased over the following 48 h. Both PCCs reversed apixaban's effect on TGA peak height, PT, and INR. Apixaban pharmacokinetic and anti-FXa profiles were consistent across treatments. Conclusions Cofact and Beriplex reversed apixaban's steady-state effects on several coagulation assessments. © 2017 International Society on Thrombosis and Haemostasis.

A superior bright NIR luminescent nanoparticle preparation and indicating calcium signaling detection in cells and small animals.

PubMed

Zhang, Jian; Lakowicz, Joseph R

2018-01-01

Near-field fluorescence (NFF) effects were employed to develop a novel near-infrared (NIR) luminescent nanoparticle (LNP) with superior brightness. The LNP is used as imaging contrast agent for cellular and small animal imaging and furthermore suggested to use for detecting voltage-sensitive calcium in living cells and animals with high sensitivity. NIR Indocyanine green (ICG) dye was conjugated with human serum albumin (HSA) followed by covalently binding to gold nanorod (AuNR). The AuNR displayed dual plasmons from transverse and longitudinal axis, and the longitudinal plasmon was localized at the NIR region which could efficiently couple with the excitation and emission of ICG dye leading to a largely enhanced NFF. The enhancement factor was measured to be about 16-fold using both ensemble and single nanoparticle spectral methods. As an imaging contrast agent, the ICG-HSA-Au complex (abbreviate as ICG-Au) was conjugated on HeLa cells and fluorescence cell images were recorded on a time-resolved confocal microscope. The emission signals of ICG-Au complexes were distinctly resolved as the individual spots that were observed over the cellular backgrounds due to their strong brightness as well as shortened lifetime. The LNPs were also tested to have a low cytotoxicity. The ICG-Au complexes were injected below the skin surface of mouse showing emission spots 5-fold brighter than those from the same amount of free ICG-HSA conjugates. Based on the observations in this research, the excitation and emission of NIR ICG dyes were found to be able to sufficiently couple with the longitudinal plasmon of AuNRs leading to a largely enhanced NFF. Using the LNP with super-brightness as a contrast agent, the ICG-Au complex could be resolved from the background in the cell and small animal imaging. The novel NIR LNP has also a great potential for detection of voltage-gated calcium concentration in the cell and living animal with a high sensitivity.

Complex social waves of giant honeybees provoked by a dummy wasp support the special-agent hypothesis.

PubMed

Kastberger, Gerald; Weihmann, Frank; Hoetzl, Thomas

2010-03-01

The social waves in giant honeybees termed as shimmering are more complex than mexican waves. it has been demonstrated1 that shimmering is triggered by special agents at the nest surface. in this paper, we have used a nest that originated by amalgamation of two previously separated nests and stimulated waves by a dummy wasp moved on a miniature cable car. we illustrate the plausibility of the special-agent hypothesis1 also for complex shimmering processes.

Complex social waves of giant honeybees provoked by a dummy wasp support the special-agent hypothesis

PubMed Central

Weihmann, Frank; Hoetzl, Thomas

2010-01-01

The social waves in giant honeybees termed as shimmering are more complex than mexican waves. it has been demonstrated1 that shimmering is triggered by special agents at the nest surface. in this paper, we have used a nest that originated by amalgamation of two previously separated nests and stimulated waves by a dummy wasp moved on a miniature cable car. we illustrate the plausibility of the special-agent hypothesis1 also for complex shimmering processes. PMID:20585516

Effect of chaotropes on the kinetics of iron release from ferritin by flavin nucleotides.

PubMed

Johnson, Lindsay E; Wilkinson, Tyler; Arosio, Paolo; Melman, Artem; Bou-Abdallah, Fadi

2017-12-01

Ferritins are ubiquitous multi-subunit iron storage and detoxification proteins that play a critical role in iron homeostasis. Ferrous ions that enter the protein's shell through hydrophilic channels are rapidly oxidized at dinuclear centers on the H-subunit before transfer to the protein's cavity for storage. The mechanisms of iron loading have been extensively studied, but little is known about iron mobilization. Fe(III) reduction can occur via rapid reduction by suitable reducing agents followed by chelation of Fe(II) ions or via direct and slow Fe(III) chelation. Here, the iron release kinetics from ferritin by FMNH 2 in the presence of various chaotropic agents are studied and their in-vivo physiological significance discussed. The iron release kinetics from horse and human ferritins by FMNH 2 were monitored at 522nm where the Fe(II)-bipyridine complex absorbs. The experiments were performed in the presence of different concentrations of three chaotropic agents, urea, guanidine HCl, and triton. Under our experimental conditions, iron reductive mobilization by the non-enzymatic FMN/NAD(P)H system is limited by the concentration of FMNH 2 and is independent on the type or amount of chaotropes present. Diffusion of FMNH 2 through the ferritin pores is an unlikely mechanism for ferritin iron reduction. An iron mobilization mechanism involving rapid electron transfer through the protein shell is discussed. Caution must be exercised when interpreting the kinetics of iron mobilization from ferritin using the FMN/NAD(P)H system. The kinetics are highly dependent on the amount of dissolved oxygen and the concentration of reagents used. Copyright © 2017 Elsevier B.V. All rights reserved.

Combined effect of synthetic enterocin CRL35 with cell wall, membrane-acting antibiotics and muranolytic enzymes against Listeria cells.

PubMed

Salvucci, E; Hebert, E M; Sesma, F; Saavedra, L

2010-08-01

To evaluate the inhibition effectiveness of enterocin CRL35 in combination with cell wall, membrane-acting antibiotics and muranolytic enzymes against the foodborne pathogen Listeria. Synthetic enterocin CRL35 alone and in combination with monensin, bacitracin, gramicidin, mutanolysin and lysozyme were used in this study. Minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) index assays were performed using Listeria innocua 7 and Listeria monocytogenes FBUNT as sensitive strains. Antibiotics showed positive interactions with the bacteriocin in both strains tested. On the other hand, when mutanolysin and enterocin CRL35 were added to resting cells in a buffer system, the lytic effect of mutanolysin was enhanced. However, the addition of mutanolysin showed no effect on the growth of L. innocua 7 cells in a culture medium. Moreover, mutanolysin allowed the overgrowth of L. innocua 7 cells to an OD similar to control cells in the presence of inhibitory concentration of enterocin CRL35. In contrast, the combination of lysozyme and enterocin CRL35 resulted in a 50% inhibition of the L. innocua 7 growth. Based on our results, we conclude that the combination of synthetic enterocin CRL35 with some antibiotics is effective against L. innocua 7 and L. monocytogenes FBUNT cells, and more importantly the amount of these agents to be used was considerably reduced. The effectiveness of the combination of synthetic enterocin CRL35 with muramidases seems to depend on complex environments, and more detailed studies need to be performed to elucidate this issue. Enterocin CRL35 represents a promising agent that not only can ensure the quality and safety of food but it can also be combined with several antimicrobial agents important in the medical field.

In vitro and in vivo antifungal efficacy of plant based lawsone against Fusarium oxysporum species complex.

PubMed

Dananjaya, S H S; Udayangani, R M C; Shin, Sang Yeop; Edussuriya, M; Nikapitiya, Chamilani; Lee, Jehee; De Zoysa, Mahanama

2017-08-01

Fusarium oxysporum is an ascomycete facultative fungus which generally affects to plants. However, it is recently known as a serious emerging opportunistic pathogen of human and other animals. F. oxysporum shows broad resistance to commonly used antifungal agents and therefore development of alternative therapeutic agents is required. In this study, we investigated the antifungal efficacy of plant based natural lawsone against pathogenic F. oxysporum. Antifungal susceptibility test determined the concentration dependent growth inhibition of lawsone against F. oxysporum with minimum inhibitory concentration (MIC) at 100μg/mL. Ultra-structural analysis indicates the prominent damage on cell wall of the mycelium after lawsone treatment, and suggests that it could increase the membrane permeability and disintegration of cells leading to cellular death. Propidium iodide (PI) uptake assay results showed the higher level of cell death in lawsone treated F. oxysporum which further confirms the loss of plasma membrane integrity. Also, detection of reactive oxygen species (ROS) using DCFH-DA has clearly indicated that lawsone (100μg/mL) can induce the ROS level in the filaments of F. oxysporum. MTT assay results showed the loss of viability and germination capacity of F. oxysporum spores by lawsone in concentration dependent manner. Moreover, lawsone treatment induced the mRNA expression of two autophagy related genes (ATG1 and ATG8) indicating that lawsone may activate the autophagy related pathways in F. oxysporum due to the oxidative stress generated by ROS. F. oxysporum infected zebrafish has recovered after lawsone therapy as a topical treatment suggesting that lawsone is a potential natural antifusariosis agent. Copyright © 2017 Elsevier GmbH. All rights reserved.

Complexation Effect on Redox Potential of Iron(III)-Iron(II) Couple: A Simple Potentiometric Experiment

ERIC Educational Resources Information Center

Rizvi, Masood Ahmad; Syed, Raashid Maqsood; Khan, Badruddin

2011-01-01

A titration curve with multiple inflection points results when a mixture of two or more reducing agents with sufficiently different reduction potentials are titrated. In this experiment iron(II) complexes are combined into a mixture of reducing agents and are oxidized to the corresponding iron(III) complexes. As all of the complexes involve the…

Efficacy and safety testing of mycotoxin-detoxifying agents in broilers following the European Food Safety Authority guidelines.

PubMed

Osselaere, A; Devreese, M; Watteyn, A; Vandenbroucke, V; Goossens, J; Hautekiet, V; Eeckhout, M; De Saeger, S; De Baere, S; De Backer, P; Croubels, S

2012-08-01

Contamination of feeds with mycotoxins is a worldwide problem and mycotoxin-detoxifying agents are used to decrease their negative effect. The European Food Safety Authority recently stated guidelines and end-points for the efficacy testing of detoxifiers. Our study revealed that plasma concentrations of deoxynivalenol and deepoxy-deoxynivalenol were too low to assess efficacy of 2 commercially available mycotoxin-detoxifying agents against deoxynivalenol after 3 wk of continuous feeding of this mycotoxin at concentrations of 2.44±0.70 mg/kg of feed and 7.54±2.20 mg/kg of feed in broilers. This correlates with the poor absorption of deoxynivalenol in poultry. A safety study with 2 commercially available detoxifying agents and veterinary drugs showed innovative results with regard to the pharmacokinetics of 2 antibiotics after oral dosing in the drinking water. The plasma and kidney tissue concentrations of oxytetracycline were significantly higher in broilers receiving a biotransforming agent in the feed compared with control birds. For amoxicillin, the plasma concentrations were significantly higher for broilers receiving an adsorbing agent in comparison to birds receiving the biotransforming agent, but not to the control group. Mycotoxin-detoxifying agents can thus interact with the oral bioavailability of antibiotics depending on the antibiotic and detoxifying agent, with possible adverse effects on the health of animals and humans.

Influence of water-soluble channeling agents on the release of diclofenac sodium from Irvingia malayana wax matrix tablets.

PubMed

Yotsawimonwat, Songwut; Charumanee, Suporn; Kaewvichit, Sayam; Sirithunyalug, Jakkapan; Sirisa-Ard, Panee; Piyamongkol, Sirivipa; Siangwong, Kulthawat

2017-05-01

Irvingia malayana wax (IW) is majorly composed of esters of medium chain fatty acids. Its melting point is low and closed to the body temperature. This study aimed at investigating the potential of IW as a matrix-forming agent and evaluate the effect of soluble channeling agents on the release of diclofenac sodium (DS) from IW matrix tablets. The preformulation study by infrared spectroscopy and differential scanning calorimetry showed no incompatibility between IW and DS or soluble channeling agents, namely PEG 4000, PEG 6000 and lactose. IW retarded the release of DS from the matrix tablets more efficiently than carnauba wax due to its greater hydrophobicity and its ability to become partial molten wax at 37° C. Factors affecting the release of DS from IW matrix were drug concentrations, and types and concentrations of channeling agents. The release of DS significantly improved when DS concentration reached approximately 33%. The fast dissolving channeling agent, lactose, could enhance the drug release rate more effectively than PEG 4000 and PEG 6000, respectively. The linear relationship between the DS release rate and the concentration of the chosen channeling agent, PEG 6000, was found (r 2 =0.9866).

Contrast agent enhanced pQCT of articular cartilage

NASA Astrophysics Data System (ADS)

Kallioniemi, A. S.; Jurvelin, J. S.; Nieminen, M. T.; Lammi, M. J.; Töyräs, J.

2007-02-01

The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n = 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r = -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally degraded articular cartilage in vitro. As high resolution imaging of e.g. the knee joint is possible with pQCT, the present technique may be further developed for in vivo quantification of PG depletion in osteoarthritic cartilage. However, careful in vitro and in vivo characterization of diffusion mechanics and optimal contrast agent concentrations are needed before diagnostic applications are feasible.

Effect of the different chain transfer agents on molecular weight and optical properties of poly(methyl methacrylate)

NASA Astrophysics Data System (ADS)

Çetinkaya, Onur; Demirci, Gökhan; Mergo, Paweł

2017-08-01

Investigation of molecular weight and optical properties of poly(methyl metacrylate) (PMMA) polymerized in house with different chain transfer agents was studied. Isopropyl alcohol (IPA), n-butyl mercaptan (nBMC) and pentamethyl disilane (PMDS) were used as chain transfer agents. The molecular weight (Mw) of PMMA samples were measured by Ostwald viscometer. Mw of bulk polymer samples were decreased with increase the concentration of chain transfer agents (CTA). Since reactivity of used CTAs is not same, molecular weights of samples which were produced with different type of CTA but same concentration of CTA was varied. Higher concentration of n-BMC showed higher scattering. Transmission of samples could not be correlated with different concentration of CTA. Refractive index of samples was not affected by concentration of CTA nevertheless higher molecular weight of CTA showed higher refractive index.

Multidrug-resistant Fusarium in keratitis: a clinico-mycological study of keratitis infections in Chennai, India.

PubMed

Tupaki-Sreepurna, Ananya; Al-Hatmi, Abdullah M S; Kindo, Anupma J; Sundaram, Murugan; de Hoog, G Sybren

2017-04-01

In this study, we aimed to present the first molecular epidemiological data from Chennai, India, analyse keratitis cases that have been monitored in a university hospital during 2 years, identify the responsible Fusarium species and determine antifungal susceptibilities. A total of 10 cases of keratitis were included in the study. Fusarium isolates were identified using the second largest subunit of the RNA polymerase gene (RPB2) and the translation elongation factor 1 alpha (TEF1). Antifungal susceptibility was tested by the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) methodology. The aetiological agents belonged to Fusarium solani species complex (FSSC) (n = 9) and Fusarium sambucinum species complex (FSAMSC) (n = 1), and the identified species were Fusarium keratoplasticum (n = 7), Fusarium falciforme (n = 2) and Fusarium sporotrichioides (n = 1). All strains showed multidrug resistance to azoles and caspofungin but exhibited lower minimum inhibitory concentration (MIC) to natamycin and amphotericin B. Fusarium keratoplasticum and Fusarium falciforme belonging to the Fusarium solani species complex were the major aetiological agents of Fusarium keratitis in this study. Early presentation and 5% topical natamycin was associated with better patient outcome. Preventative measures and monitoring of local epidemiological data play an important role in clinical practice. © 2016 Blackwell Verlag GmbH.

Competitive FRET-aptamer-based detection of methylphosphonic acid, a common nerve agent metabolite.

PubMed

Bruno, John G; Carrillo, Maria P; Phillips, Taylor; Vail, Neal K; Hanson, Douglas

2008-09-01

Competitive fluorescence resonance energy transfer (FRET)-aptamer-based assay formats are described for one-step detection of methylphosphonic acid (MPA; a metabolite of several organophosphorus (OP) nerve agents). AminoMPA was attached to tosyl-magnetic beads and used for DNA aptamer selection from which one dominant aptamer sequence emerged. Two different FRET approaches were attempted. In one approach, the complementary DNA sequence was used as a template for labeling the aptamer with Alexa Fluor 546 (AF 546)-14-dUTP by asymmetric PCR. Following 3-dimensional (3-D), molecular modeling of the aptamer-MPA complex, a series of three fluoresceinated aptamers labeled at positions 50, 51, and 52 in the putative optimal binding pocket were synthesized. In both FRET formats, aminoMPA was linked to Black Hole Quencher (BHQ-1 or BHQ-2)-succinimides and allowed to bind the fluorescein or AF 546-labeled MPA aptamer. Following gel filtration to purify the labeled MPA aptamer-BHQ-aminoMPA FRET complexes, the complexes were competed against various concentrations of unlabeled MPA, MPA derivatives, and unrelated compounds in titration and cross-reactivity studies. Both approaches yielded low microgram per milliliter detection limits for MPA with generally low levels of cross-reactivity for unrelated compounds. However, the data suggest a pattern of traits that may effect the direction (lights on or off) and intensity of the FRET.

Ontology of Earth's nonlinear dynamic complex systems

NASA Astrophysics Data System (ADS)

Babaie, Hassan; Davarpanah, Armita

2017-04-01

As a complex system, Earth and its major integrated and dynamically interacting subsystems (e.g., hydrosphere, atmosphere) display nonlinear behavior in response to internal and external influences. The Earth Nonlinear Dynamic Complex Systems (ENDCS) ontology formally represents the semantics of the knowledge about the nonlinear system element (agent) behavior, function, and structure, inter-agent and agent-environment feedback loops, and the emergent collective properties of the whole complex system as the result of interaction of the agents with other agents and their environment. It also models nonlinear concepts such as aperiodic, random chaotic behavior, sensitivity to initial conditions, bifurcation of dynamic processes, levels of organization, self-organization, aggregated and isolated functionality, and emergence of collective complex behavior at the system level. By incorporating several existing ontologies, the ENDCS ontology represents the dynamic system variables and the rules of transformation of their state, emergent state, and other features of complex systems such as the trajectories in state (phase) space (attractor and strange attractor), basins of attractions, basin divide (separatrix), fractal dimension, and system's interface to its environment. The ontology also defines different object properties that change the system behavior, function, and structure and trigger instability. ENDCS will help to integrate the data and knowledge related to the five complex subsystems of Earth by annotating common data types, unifying the semantics of shared terminology, and facilitating interoperability among different fields of Earth science.

Correlation between the enhancement of flunitrazepam binding by GABA and seizure susceptibility in mice

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

Marley, R.J.; Wehner, J.M.

Various populations of mice exhibit differential sensitivity to seizure-inducing agents. The relationship of seizure susceptibility to alterations in the GABA receptor complex was investigated in six different populations of mice consisting of four inbred strains (C57BL, DBA, C3H, and BALB) and two selected lines (long sleep and short sleep). Seizure activity was induced by intraperitoneal administration of the GAD inhibitor, 3-mercaptopropionic acid, and latencies to seizure onset and tonus were measured. In naive mice of the same populations, GABA enhancement of TH-flunitrazepam binding was measured in extensively washed whole brain membranes at several GABA concentrations. Both differential seizure sensitivity tomore » 3-mercaptopropionic acid and differential enhancement of TH-flunitrazepam binding by GABA were observed in these six populations of mice. Correlational analyses indicated a positive correlation between the degree of GABA enhancement of TH-flunitrazepam binding and resistance to the seizure-inducing properties of 3-mercaptopropionic acid. These data suggest that genetic differences in sensitivity to seizure-inducing agents that disrupt the GABAergic system may be related to differences in coupling between the various receptors associated with the GABA receptor complex.« less

Growth mechanisms of MgO nanocrystals via a sol-gel synthesis using different complexing agents

PubMed Central

2014-01-01

In the preparation of nanostructured materials, it is important to optimize synthesis parameters in order to obtain the desired material. This work investigates the role of complexing agents, oxalic acid and tartaric acid, in the production of MgO nanocrystals. Results from simultaneous thermogravimetric analysis (STA) show that the two different synthesis routes yield precursors with different thermal profiles. It is found that the thermal profiles of the precursors can reveal the effects of crystal growth during thermal annealing. X-ray diffraction confirms that the final products are pure, single phase and of cubic shape. It is also found that complexing agents can affect the rate of crystal growth. The structures of the oxalic acid and tartaric acid as well as the complexation sites play very important roles in the formation of the nanocrystals. The complexing agents influence the rate of growth which affects the final crystallite size of the materials. Surprisingly, it is also found that oxalic acid and tartaric acid act as surfactants inhibiting crystal growth even at a high temperature of 950°C and a long annealing time of 36 h. The crystallite formation routes are proposed to be via linear and branched polymer networks due to the different structures of the complexing agents. PMID:24650322

Chemical Action of Halogenated Agents in Fire Extinguishing

NASA Technical Reports Server (NTRS)

Belles, Frank E.

1955-01-01

The action of halogenated agents in preventing flame propagation in fuel-air mixtures in laboratory tests is discussed in terms of a possible chemical mechanism. The mechanism chosen is that of chain-breaking reactions between agent and active particles (hydrogen and oxygen atoms and hydroxyl radicsls). Data from the literature on the flammability peaks of n-heptane agent-air mixtures are treated. Ratings of agent effectiveness in terms of the fuel equivalent of the agent, based on both fuel and agent concentrations at the peak, are proposed as preferable to ratings in terms of agent concentration alone. These fuel-equivalent ratings are roughly correlated by reactivities assigned to halogen and hydrogen atoms in the agent molecules. It is concluded that the presence of hydrogen in agent need not reduce its fire-fighting ability, provided there is enough halogen to make the agent nonflammable. A method is presented for estimating from quenching-distance data a rate constant for the reaction of agent with active particles. A quantitative result is obtained for methyl bromide. This rate constant predicts the observed peak concentration of methyl bromide quite well. However, more data are needed to prove the validity of the method. The assumption that hal.ogenatedagents act mainly by chain-bresking reactions with active particles is consistent with the experimental facts and should help guide the selection of agents for further tests.

Preparation and self-sterilizing properties of Ag@TiO2-styrene-acrylic complex coatings.

PubMed

Zhou, Xiang-dong; Chen, Feng; Yang, Jin-tao; Yan, Xiao-hui; Zhong, Ming-qiang

2013-04-01

In this study, we report a simple and cost-effective method for self-sterilized complex coatings obtained by Ag@TiO2 particle incorporation into styrene-acrylic latex. The Ag@TiO2 particles were prepared via a coupling agent modification process. The composite latices characterized by transmission electron microscopy (TEM) study were highly homogeneous at the nanometric scale, and the Ag@TiO2 particles were well dispersed and exhibited an intimate contact between both the organic and inorganic components. The Ag@TiO2 nanoparticles significantly enhanced the absorption in the visible region and engendered a good heat-insulating effect of the complex coatings. Moreover, the Ag@TiO2 nanoparticle incorporation into this polymer matrix renders self-sterilized nanocomposite materials upon light excitation, which are tested against Escherichia coli and Staphylococcus aureus. The complex coatings display an impressive performance in the killing of all micro-organisms with a maximum for a Ag@TiO2 loading concentration of 2-5 wt.%. The weathering endurance of the complex coating was also measured. Copyright © 2012 Elsevier B.V. All rights reserved.

Gallic acid/hydroxypropyl-β-cyclodextrin complex: Improving solubility for application on in vitro/ in vivo Candida albicans biofilms

PubMed Central

Teodoro, Guilherme Rodrigues; Salvador, Marcos José; Koga-Ito, Cristiane Yumi

2017-01-01

The aim of this study was to increase the solubility of gallic acid (GA) for the treatment of Candida albicans biofilm, which is very difficult to treat and requires high drug concentrations. Cyclodextrins (CDs) were used for this purpose. Complexes were evaluated by phase-solubility studies, prepared by spray drying and characterized by drug loading, scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The complexes were tested on C. albicans biofilm using in vitro and in vivo models. HPβCD formed soluble inclusion complexes with GA. The percentage of GA in GA/HPβCD was 10.8 ± 0.01%. The SEM and DSC analyses confirmed the formation of inclusion complexes. GA/HPβCD maintained the antimicrobial activity of the pure GA. GA/HPβCD was effective on C. albicans biofilms of 24 and 48h. The in vivo results showed an anti-inflammatory activity of GA/HPβCD with no difference in invading hypha counting among the groups. This study encourages the development of new antifungal agents. PMID:28700692

Iron-based ferritin nanocore as a contrast agent.

PubMed

Sana, Barindra; Johnson, Eric; Sheah, Kenneth; Poh, Chueh Loo; Lim, Sierin

2010-09-01

Self-assembling protein cages have been exploited as templates for nanoparticle synthesis. The ferritin molecule, a protein cage present in most living systems, stores excess soluble ferrous iron in the form of an insoluble ferric complex within its cavity. Magnetic nanocores formed by loading excess iron within an engineered ferritin from Archaeoglobus fulgidus (AfFtn-AA) were studied as a potential magnetic resonance (MR) imaging contrast agent. The self-assembly characteristics of the AfFtn-AA were investigated using dynamic light scattering technique and size exclusion chromatography. Homogeneous size distribution of the assembled nanoparticles was observed using transmission electron microscopy. The magnetic properties of iron-loaded AfFtn-AA were studied using vibrating sample magnetometry. Images obtained from a 3.0 T whole-body MRI scanner showed significant brightening of T(1) images and signal loss of T(2) images with increased concentrations of iron-loaded AfFtn-AA. The analysis of the MR image intensities showed extremely high R(2) values (5300 mM(-1) s(-1)) for the iron-loaded AfFtn-AA confirming its potential as a T(2) contrast agent.

Complex groundwater flow systems as traveling agent models

PubMed Central

Padilla, Pablo; Escolero, Oscar; González, Tomas; Morales-Casique, Eric; Osorio-Olvera, Luis

2014-01-01

Analyzing field data from pumping tests, we show that as with many other natural phenomena, groundwater flow exhibits complex dynamics described by 1/f power spectrum. This result is theoretically studied within an agent perspective. Using a traveling agent model, we prove that this statistical behavior emerges when the medium is complex. Some heuristic reasoning is provided to justify both spatial and dynamic complexity, as the result of the superposition of an infinite number of stochastic processes. Even more, we show that this implies that non-Kolmogorovian probability is needed for its study, and provide a set of new partial differential equations for groundwater flow. PMID:25337455

Adsorption study of a macro-RAFT agent onto SiO2-coated Gd2O3:Eu3+ nanorods: Requirements and limitations

NASA Astrophysics Data System (ADS)

Zou, Hua; Melro, Liliana; de Camargo Chaparro, Thaissa; de Souza Filho, Isnaldi Rodrigues; Ananias, Duarte; Bourgeat-Lami, Elodie; dos Santos, Amilton Martins; Barros-Timmons, Ana

2017-02-01

The use of a macromolecular RAFT (macro-RAFT) agent to encapsulate anisotropic nano-objects via emulsion polymerization is an emerging route to prepare polymer/inorganic colloidal nanocomposites. However, a number of requirements have to be fulfilled. This work aims at highlighting the effects of the preparative procedure and dispersion method on the amount of macro-RAFT agent adsorbed onto SiO2-coated Gd2O3:Eu3+ nanorods. The adsorption of macro-RAFT agent was studied using the depletion method with UV-vis spectrophotometry. Measurements were performed at a fixed concentration of nanorods and varying concentrations of the macro-RAFT agent in aqueous dispersion at room temperature. The adsorption isotherms showed that for the same initial macro-RAFT agent concentration, the highest adsorption capacity of the macro-RAFT agent on nanorods was usually achieved for non-calcined thin SiO2-coated nanorods under mild bath sonication.

Hydrophilic nano-silica coating agents with platinum and diamond nanoparticles for denture base materials.

PubMed

Yoshizaki, Taro; Akiba, Norihisa; Inokoshi, Masanao; Shimada, Masayuki; Minakuchi, Shunsuke

2017-05-31

Preventing microorganisms from adhering to the denture surface is important for ensuring the systemic health of elderly denture wearers. Silica coating agents provide high hydrophilicity but lack durability. This study investigated solutions to improve the durability of the coating layer, determine an appropriate solid content concentration of SiO 2 in the silica coating agent, and evaluate the effect of adding platinum (Pt) and diamond nanoparticles (ND) to the agent. Five coating agents were prepared with different SiO 2 concentrations with/without Pt and ND additives. The contact angle was measured, and the brush-wear test was performed. Scanning electron microscopy was used to investigate the silica coating layer. The appropriate concentration of SiO 2 was found to be 0.5-0.75 wt%. The coating agents with additives showed significantly high hydrophilicity immediately after coating and after the brush-wear test. The coating agents with/without additives formed a durable coating layer even after the brush-wear test.

Weathering and evaporation controls on dissolved uranium concentrations in groundwater - A case study from northern Burundi.

PubMed

Post, V E A; Vassolo, S I; Tiberghien, C; Baranyikwa, D; Miburo, D

2017-12-31

The potential use of groundwater for potable water supply can be severely compromised by natural contaminants such as uranium. The environmental mobility of uranium depends on a suite of factors including aquifer lithology, redox conditions, complexing agents, and hydrological processes. Uranium concentrations of up to 734μg/L are found in groundwater in northern Burundi, and the objective of the present study was to identify the causes for these elevated concentrations. Based on a comprehensive data set of groundwater chemistry, geology, and hydrological measurements, it was found that the highest dissolved uranium concentrations in groundwater occur near the shores of Lake Tshohoha South and other smaller lakes nearby. A model is proposed in which weathering and evapotranspiration during groundwater recharge, flow and discharge exert the dominant controls on the groundwater chemical composition. Results of PHREEQC simulations quantitatively confirm this conceptual model and show that uranium mobilization followed by evapo-concentration is the most likely explanation for the high dissolved uranium concentrations observed. The uranium source is the granitic sand, which was found to have a mean elemental uranium content of 14ppm, but the exact mobilization process could not be established. Uranium concentrations may further be controlled by adsorption, especially where calcium-uranyl‑carbonate complexes are present. Water and uranium mass balance calculations for Lake Tshohoha South are consistent with the inferred fluxes and show that high‑uranium groundwater represents only a minor fraction of the overall water input to the lake. These findings highlight that the evaporation effects that cause radionuclide concentrations to rise to harmful levels in groundwater discharge areas are not only confined to arid regions, and that this should be considered when selecting suitable locations for water supply wells. Copyright © 2017 Elsevier B.V. All rights reserved.

Pathways for the Oxidation of Sarin in Urban Atmospheres

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

Gerald E. Streit; James E. Bossert; Jeffrey S. Gaffney

1998-11-01

Terrorists have threatened and carried out chemicalhiological agent attacks on targets in major cities. The nerve agent sarin figured prominently in one well-publicized incident. Vapors disseminating from open containers in a Tokyo subway caused thousands of casualties. High-resolution tracer transport modeling of agent dispersion is at hand and will be enhanced by data on reactions with components of the urban atmosphere. As a sample of the level of complexity currently attainable, we elaborate the mechanisms by which sarin can decompose in polluted air. A release scenario is outlined involving the passage of a gas-phase agent through a city locale inmore » the daytime. The atmospheric chemistry database on related organophosphorus pesticides is mined for rate and product information. The hydroxyl,radical and fine-mode particles are identified as major reactants. A review of urban air chernistry/rnicrophysics generates concentration tables for major oxidant and aerosol types in both clean and dirty environments. Organic structure-reactivity relationships yield an upper limit of 10-1' cm3 molecule-' S-* for hydrogen abstraction by hydroxyl. The associated midday loss time scale could be as little as one hour. Product distributions are difficult to define but may include nontoxic organic oxygenates, inorganic phosphorus acids, sarin-like aldehydes, and nitrates preserving cholinergic capabilities. Agent molecules will contact aerosol surfaces in on the order of minutes, with hydrolysis and side-chain oxidation as likely reaction channels.« less

Physics-based agent to simulant correlations for vapor phase mass transport.

PubMed

Willis, Matthew P; Varady, Mark J; Pearl, Thomas P; Fouse, Janet C; Riley, Patrick C; Mantooth, Brent A; Lalain, Teri A

2013-12-15

Chemical warfare agent simulants are often used as an agent surrogate to perform environmental testing, mitigating exposure hazards. This work specifically addresses the assessment of downwind agent vapor concentration resulting from an evaporating simulant droplet. A previously developed methodology was used to estimate the mass diffusivities of the chemical warfare agent simulants methyl salicylate, 2-chloroethyl ethyl sulfide, di-ethyl malonate, and chloroethyl phenyl sulfide. Along with the diffusivity of the chemical warfare agent bis(2-chloroethyl) sulfide, the simulant diffusivities were used in an advection-diffusion model to predict the vapor concentrations downwind from an evaporating droplet of each chemical at various wind velocities and temperatures. The results demonstrate that the simulant-to-agent concentration ratio and the corresponding vapor pressure ratio are equivalent under certain conditions. Specifically, the relationship is valid within ranges of measurement locations relative to the evaporating droplet and observation times. The valid ranges depend on the relative transport properties of the agent and simulant, and whether vapor transport is diffusion or advection dominant. Published by Elsevier B.V.

Impact of urban development on the chemical composition of ground water in a fen-wetland complex

USGS Publications Warehouse

Panno, S.V.; Nuzzo, V.A.; Cartwright, K.; Hensel, B.R.; Krapac, I.G.

1999-01-01

A 15-month-long hydrogeologic investigation of a fen-wetland complex in northeastern Illinois, USA indicated the encroachment of ground-water-borne anthropogenic contaminants into two of three high quality fens. Ground-water flow directions and chemical evidence indicated that plumes of ground water with anomalously large concentrations of Na+ and Cl- originated from a private septic system and from rock salt spread on an adjacent road. The contamination, in turn, had an adverse effect on fen vegetation; within the plumes, diverse vegetation was replaced by the more salt-tolerant narrow-leaf cattail (Typha angustifolia). Ground water of the third fen contained large concentrations of SO42- as high as 516 mg/L. The SO42- anomaly was observed on a transient and/or seasonal basis in the fen ground water and in an adjacent marsh and pond. Isotopically light ??34S values in these waters indicated that the addition of SO42- resulted from the oxidation of pyrite within underlying peat and/or pyritic gravel. However, the large SO42- concentrations had no discernible effect on fen vegetation. The results of this investigation indicate how easily construction of houses with private septic systems and deicing agents from roadway maintenance can contaminate fen ground water with relatively large concentrations of Na+ and Cl-, resulting in a significant loss of biodiversity in fens.

Stability of actin-lysozyme complexes formed in cystic fibrosis disease.

PubMed

Mohammadinejad, Sarah; Ghamkhari, Behnoush; Abdolmaleki, Sarah

2016-08-21

Finding the conditions for destabilizing actin-lysozyme complexes is of biomedical importance in preventing infections in cystic fibrosis. In this manuscript, the effects of different charge-mutants of lysozyme and salt concentration on the stability of actin-lysozyme complexes are studied using Langevin dynamics simulation. A coarse-grained model of F-actin is used in which both its twist and bending rigidities are considered. We observe that the attraction between F-actins is stronger in the presence of wild-type lysozymes relative to the mutated lysozymes of lower charges. By calculating the potential of mean force between F-actins, we conclude that the stability of actin-lysozyme complexes is decreased by reducing the charge of lysozyme mutants. The distributions of different lysozyme charge-mutants show that wild-type (+9e) lysozymes are mostly accumulated in the center of triangles formed by three adjacent F-actins, while lysozyme mutants of charges +7e and +5e occupy the bridging regions between F-actins. Low-charge mutants of lysozyme (+3e) distribute uniformly around F-actins. A rough estimate of the electrostatic energy for these different distributions proves that the distribution in which lysozymes reside in the center of triangles leads to more stable complexes. Also our results in the presence of a salt suggest that at physiological salt concentration of airway, F-actin complexes are not formed by charge-reduced mutants of lysozyme. The findings are interesting because if we can design charge-reduced lysozyme mutants with considerable antibacterial activity, they are not sequestered inside F-actin aggregates and can play their role as antibacterial agents against airway infection.

Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9.

PubMed Central

Curtet, C; Tellier, C; Bohy, J; Conti, M L; Saccavini, J C; Thedrez, P; Douillard, J Y; Chatal, J F; Koprowski, H

1986-01-01

Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium X diethylenetriaminepentaacetic acid (Gd X DTPA) and used as a contrast agent in nuclear magnetic resonance (NMR) in an effort to improve tumor target selectivity in nude mice. The data indicate that Gd X DTPA-mAb 19-9 in solution decreased the T1 relaxation of water protons at 90 MHz in direct proportion to the gadolinium concentration, and this effect was greater than in Gd X DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of Gd X DTPA-mAb 19-9 (Gd, 20 mumol/kg; 16 DTPA molecules per mAb molecule), was significantly decreased (by 15%) as compared with the control group. Similar results were obtained in tumors from mice injected with Gd X DTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 mumol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for Gd X DTPA (10-100 mumol/kg) as contrast agent. Tumor localization by the Gd X DTPA-mAb 19-9 complex containing radioactive Gd (0.3 microCi/microgram of 153Gd) to confirm scintigraphy revealed significant concentrations of the complex (5% of the injected dose per gram of tissue) in the tumor. Scan images recorded in planar scintigraphy at day 5 showed good visualization of tumors. Images PMID:3459174

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

Hannachi, Amira, E-mail: amira.hannachi88@gmail.com; Maghraoui-Meherzi, Hager

Manganese sulfide thin films have been deposited on glass slides by chemical bath deposition (CBD) method. The effects of preparative parameters such as deposition time, bath temperature, concentration of precursors, multi-layer deposition, different source of manganese, different complexing agent and thermal annealing on structural and morphological film properties have been investigated. The prepared thin films have been characterized using the X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). It exhibit the metastable forms of MnS, the hexagonal γ-MnS wurtzite phase with preferential orientation in the (002) plane or the cubic β-MnS zinc blende with preferentialmore » orientation in the (200) plane. Microstructural studies revealed the formation of MnS crystals with different morphologies, such as hexagons, spheres, cubes or flowers like. - Graphical Abstract: We report the preparation of different phases of manganese sulfide thin films (γ, β and α-MnS) by chemical bath deposition method. The effects of deposition parameters such as deposition time and temperature, concentrations of precursors and multi-layer deposition on MnS thin films structure and morphology were investigated. The influence of thermal annealing under nitrogen atmosphere at different temperature on MnS properties was also studied. Different manganese precursors as well as different complexing agent were also used. - Highlights: • γ and β-MnS films were deposited on substrate using the chemical bath deposition. • The effect of deposition parameters on MnS film properties has been investigated. • Multi-layer deposition was also studied to increase film thickness. • The effect of annealing under N{sub 2} at different temperature was investigated.« less

Determination of ethylenediaminetetraacetic acid in sea water by solid-phase extraction and high-performance liquid chromatography.

PubMed

Kemmei, Tomoko; Kodama, Shuji; Fujishima, Hironori; Yamamoto, Atsushi; Inoue, Yoshinori; Hayakawa, Kazuichi

2012-01-04

The chelating agent EDTA is widely used, and as a result is showing up widely in the aquatic environment. Here we describe a preconcentration procedure for measuring EDTA concentration in sea water samples by HPLC. The procedure consists of forming an Fe(III) complex followed by solid-phase extraction using an activated carbon cartridge. After the preconcentration, EDTA was quantified by HPLC with ultraviolet detection (260 nm). The enrichment permitted the determination of EDTA at concentrations as low as 1 nM. Good recoveries were obtained for both brackish and full-strength sea water with high repeatability (RSD<6%). The method was applied to sea water samples taken from near the mouth of the Oyabe River in Japan. Copyright © 2011 Elsevier B.V. All rights reserved.

Persistence and potential effects of complex organic contaminant mixtures in wastewater-impacted streams

USGS Publications Warehouse

Barber, Larry B.; Keefe, Steffanie H.; Brown, Greg K.; Furlong, Edward T.; Gray, James L.; Kolpin, Dana W.; Meyer, Michael T.; Sandstrom, Mark W.; Zaugg, Steven D.

2013-01-01

Natural and synthetic organic contaminants in municipal wastewater treatment plant (WWTP) effluents can cause ecosystem impacts, raising concerns about their persistence in receiving streams. In this study, Lagrangian sampling, in which the same approximate parcel of water is tracked as it moves downstream, was conducted at Boulder Creek, Colorado and Fourmile Creek, Iowa to determine in-stream transport and attenuation of organic contaminants discharged from two secondary WWTPs. Similar stream reaches were evaluated, and samples were collected at multiple sites during summer and spring hydrologic conditions. Travel times to the most downstream (7.4 km) site in Boulder Creek were 6.2 h during the summer and 9.3 h during the spring, and to the Fourmile Creek 8.4 km downstream site times were 18 and 8.8 h, respectively. Discharge was measured at each site, and integrated composite samples were collected and analyzed for >200 organic contaminants including metal complexing agents, nonionic surfactant degradates, personal care products, pharmaceuticals, steroidal hormones, and pesticides. The highest concentration (>100 μg L–1) compounds detected in both WWTP effluents were ethylenediaminetetraacetic acid and 4-nonylphenolethoxycarboxylate oligomers, both of which persisted for at least 7 km downstream from the WWTPs. Concentrations of pharmaceuticals were lower (<1 μg L–1), and several compounds, including carbamazepine and sulfamethoxazole, were detected throughout the study reaches. After accounting for in-stream dilution, a complex mixture of contaminants showed little attenuation and was persistent in the receiving streams at concentrations with potential ecosystem implications.

Synthesis of sulfadimethoxine based surfactants and their evaluation as antitumor agents.

PubMed

Khowdiary, Manal Mohmed; Mostafa, Nashwa S

2016-01-01

Synthesized CO (II) and Pt (II) of sulfadimethoxine. These compounds were tested for potential antitumor activity against two of human tumor cell lines, colon carcinoma cell line [Hct116], and breast carcinoma cell line MCF7. The structures of the resulting compounds have been investigated by elemental, FT-IR and H 1 NMR analyzes to insure the purity and confirmed the structures of them. The surface properties studies and octanol/water partition coefficients, Po/w were measured. The synthesized compounds exhibit biological activities with the lowest log Po/w and critical micelle concentration (CMC) values. In addition, in this article we provide an insight into this subject in order to increase the drug bioavailability. Inhibitory activity against colon carcinoma cells was detected for Pt and cobalt ion complex with IC50 = 4.5, 2.2 µg and against breast carcinoma cells IC50 = 18.2, 5.7 µg, respectively. The main goal of cancer therapy is to attain the maximum therapeutic damage of tumor cells in combination with a minimum concentration of the drug. This can be achieved in principle via selective antitumor preparations, the cytostatic effects of which would be restricted within tumor tissue. While 100% selectivity may be impractical, the achievement of reasonably high selectivity seems to be a feasible aim. Platinum and cobalt complex surfactants in our research affect tumor tissue at a very low concentration at values lower than their CMC values; this indicate that the sulfadimethoxine complexes merit further investigation as potential antitumor drugs.

Fire Extinguishing Agents, Aqueous Film Forming Foam (AFFF) Liquid Concentration Partial Percentage

DTIC Science & Technology

1989-08-31

AFFF concentrations. aqueous film forming foam , AFFF , firefighting ...Extinguishing Agents, Aqueous Film Forming Foam ( AFFF ) Liquid Concentration Partial Percentage F08637-88-C-0067 06022104F 2104 30 21043034 Applied Research...objective of this test series was to qualify 3/4 and 1 percent Aqueous Film Forming Foam ( AFFF ) concentrate for use in Air Force fire fighting

New insights in the pathogenesis of atopic disease.

PubMed

Ionescu, John G

2009-01-01

A causal link between the increasing environmental pollution and the fast spreading of allergic diseases is currently discussed. The exogenic and endogenic noxious agents contributing to the total environmental load are primarily acting through immunotoxic, sensitizing and neurotoxic mechanisms in animal experiments and in humans. Beside classic allergic-triggering factors (allergen potency, intermittent exposure to different allergen concentrations, presence of microbial bodies and sensitizing phenols), the adjuvant role of environmental pollutants gains increasing importance in allergy induction. Our therapy experience with more than 18.000 atopic eczema patients shows that beside allergic reactions pseudoallergic mechanisms through toxic environmental agents (formaldehyde, industrial and traffic smog, wood preservatives, microbial toxins, additive-rich food, nicotine, alcohol, pesticides, solvents, amalgam-heavy metals) are increasingly incriminated as causal factors for the complex symptomatology. The avoidance and elimination of such triggering factors before and during pregnancy and in early childhood may result in a significant decrease of the incidence of atopic diseases.

New Insights in the Pathogenesis of Atopic Disease

PubMed Central

Ionescu, GJ

2009-01-01

A causal link between the increasing environmental pollution and the fast spreading of allergic diseases is currently discussed. The exogenic and endogenic noxious agents contributing to the total environmental load are primarily acting through immunotoxic, sensitizing and neurotoxic mechanisms in animal experiments and in humans. Beside classic allergic–triggering factors (allergen potency, intermittent exposure to different allergen concentrations, presence of microbial bodies and sensitizing phenols), the adjuvant role of environmental pollutants gains increasing importance in allergy induction. Our therapy experience with more than 18.000 atopic eczema patients shows that beside allergic reactions pseudoallergic mechanisms through toxic environmental agents (formaldehyde, industrial and traffic smog, wood preservatives, microbial toxins, additive–rich food, nicotine, alcohol, pesticides, solvents, amalgam–heavy metals) are increasingly incriminated as causal factors for the complex symptomatology. The avoidance and elimination of such triggering factors before and during pregnancy and in early childhood may result in a significant decrease of the incidence of atopic diseases.

New Insights in the Pathogenesis of Atopic Disease

PubMed Central

John G., Ionescu

2009-01-01

A causal link between the increasing environmental pollution and the fast spreading of allergic diseases is currently discussed. The exogenic and endogenic noxious agents contributing to the total environmental load are primarily acting through immunotoxic, sensitizing and neurotoxic mechanisms in animal experiments and in humans. Beside classic allergic-triggering factors (allergen potency, intermittent exposure to different allergen concentrations, presence of microbial bodies and sensitizing phenols), the adjuvant role of environmental pollutants gains increasing importance in allergy induction. Our therapy experience with more than 18.000 atopic eczema patients shows that beside allergic reactions pseudoallergic mechanisms through toxic environmental agents (formaldehyde, industrial and traffic smog, wood preservatives, microbial toxins, additive-rich food, nicotine, alcohol, pesticides, solvents, amalgam-heavy metals) are increasingly incriminated as causal factors for the complex symptomatology. The avoidance and elimination of such triggering factors before and during pregnancy and in early childhood may result in a significant decrease of the incidence of atopic diseases. PMID:20108533

Phosphate binder usage in kidney failure patients.

PubMed

Bleyer, Anthony J

2003-06-01

Phosphorus binders are used in patients with kidney failure because of the incomplete removal of phosphorus with dialysis and the inability to exclude phosphorus from the diet. Aluminium was the initial phosphorus binder used, but was replaced by calcium-containing binders because of the development of aluminium toxicity. Calcium-based binders have been the mainstay of therapy for many years, but recent investigations have pointed to increased rates of vascular calcification in patients taking calcium-containing binders. For this reason, alternative agents have been developed. Sevelamer (Renagel), GelTex Pharmaceuticals Inc.) is a polymer which has been found to effectively bind phosphorus. It has resulted in a decreased rate of vascular calcification compared to calcium-containing binders. Other agents under development include lanthanum carbonate and iron-complex preparations. Further research will likely concentrate on identifying binders that bind phosphate more efficiently, have minimal gastrointestinal side effects and provide other benefits to dialysis patients.

Facile fabrication of high-quality Ag/PS coaxial nanocables based on the mixed mode of soft/hard templates

NASA Astrophysics Data System (ADS)

Wan, Mimi; Zhao, Wenbo; Peng, Fang; Wang, Qi; Xu, Ping; Mao, Chun; Shen, Jian

2016-08-01

A new kind of high-quality Ag/PS coaxial nanocables can be facilely synthesized by using soft/hard templates method. In order to effectively introduce Ag sources into porous polystyrene (PS) nanotubes which were trapped in porous anodic aluminum oxide (AAO) hard template, Pluronic F127 (F127) was used as guiding agent, soft template and reductant. Meanwhile, ethylene glycol solution was also used as solvent and co-reducing agent to assist in the formation of silver nanowires. The influences of concentration of F127 and reducing reaction time on the formation of Ag/PS coaxial nanocables were discussed. Results indicated that the high-quality Ag/PS coaxial nanocables can be obtained by the mixed mode of soft/hard templates under optimized conditions. This strategy is expected to be extended to design more metal/polymer coaxial nanocables for the benefit of creation of complex and functional nanoarchitectures and components.

Multi-Agent simulation of generation capacity expansion decisions.

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

Botterud, A.; Mahalik, M.; Conzelmann, G.

2008-01-01

In this paper, we use a multi-agent simulation model, EMCAS, to analyze generation expansion in the Iberian electricity market. The expansion model simulates generation investment decisions of decentralized generating companies (GenCos) interacting in a complex, multidimensional environment. A probabilistic dispatch algorithm calculates prices and profits for new candidate units in different future states of the system. Uncertainties in future load, hydropower conditions, and competitorspsila actions are represented in a scenario tree, and decision analysis is used to identify the optimal expansion decision for each individual GenCo. We run the model using detailed data for the Iberian market. In a scenariomore » analysis, we look at the impact of market design variables, such as the energy price cap and carbon emission prices. We also analyze how market concentration and GenCospsila risk preferences influence the timing and choice of new generating capacity.« less

Internet-enabled collaborative agent-based supply chains

NASA Astrophysics Data System (ADS)

Shen, Weiming; Kremer, Rob; Norrie, Douglas H.

2000-12-01

This paper presents some results of our recent research work related to the development of a new Collaborative Agent System Architecture (CASA) and an Infrastructure for Collaborative Agent Systems (ICAS). Initially being proposed as a general architecture for Internet based collaborative agent systems (particularly complex industrial collaborative agent systems), the proposed architecture is very suitable for managing the Internet enabled complex supply chain for a large manufacturing enterprise. The general collaborative agent system architecture with the basic communication and cooperation services, domain independent components, prototypes and mechanisms are described. Benefits of implementing Internet enabled supply chains with the proposed infrastructure are discussed. A case study on Internet enabled supply chain management is presented.

A fuzzy logic control in adjustable autonomy of a multi-agent system for an automated elderly movement monitoring application.

PubMed

Mostafa, Salama A; Mustapha, Aida; Mohammed, Mazin Abed; Ahmad, Mohd Sharifuddin; Mahmoud, Moamin A

2018-04-01

Autonomous agents are being widely used in many systems, such as ambient assisted-living systems, to perform tasks on behalf of humans. However, these systems usually operate in complex environments that entail uncertain, highly dynamic, or irregular workload. In such environments, autonomous agents tend to make decisions that lead to undesirable outcomes. In this paper, we propose a fuzzy-logic-based adjustable autonomy (FLAA) model to manage the autonomy of multi-agent systems that are operating in complex environments. This model aims to facilitate the autonomy management of agents and help them make competent autonomous decisions. The FLAA model employs fuzzy logic to quantitatively measure and distribute autonomy among several agents based on their performance. We implement and test this model in the Automated Elderly Movements Monitoring (AEMM-Care) system, which uses agents to monitor the daily movement activities of elderly users and perform fall detection and prevention tasks in a complex environment. The test results show that the FLAA model improves the accuracy and performance of these agents in detecting and preventing falls. Copyright © 2018 Elsevier B.V. All rights reserved.

Polydisulfide Manganese(II) Complexes as Non-Gadolinium Biodegradable Macromolecular MRI Contrast Agents

PubMed Central

Ye, Zhen; Jeong, Eun-Kee; Wu, Xueming; Tan, Mingqian; Yin, Shouyu; Lu, Zheng-Rong

2011-01-01

Purpose To develop safe and effective manganese(II) based biodegradable macromolecular MRI contrast agents. Materials and Methods In this study, we synthesized and characterized two polydisulfide manganese(II) complexes, Mn-DTPA cystamine copolymers and Mn-EDTA cystamine copolymers, as new biodegradable macromolecular MRI contrast agents. The contrast enhancement of the two manganese based contrast agents were evaluated in mice bearing MDA-MB-231 human breast carcinoma xenografts, in comparison with MnCl2. Results The T1 and T2 relaxivities were 4.74 and 10.38 mM−1s−1 per manganese at 3T for Mn-DTPA cystamine copolymers (Mn=30.50 kDa) and 6.41 and 9.72 mM−1s−1 for Mn-EDTA cystamine copolymers (Mn= 61.80 kDa). Both polydisulfide Mn(II) complexes showed significant liver, myocardium and tumor enhancement. Conclusion The manganese based polydisulfide contrast agents have a potential to be developed as alternative non-gadolinium contrast agents for MR cancer and myocardium imaging. PMID:22031457

Active Brownian agents with concentration-dependent chemotactic sensitivity.

PubMed

Meyer, Marcel; Schimansky-Geier, Lutz; Romanczuk, Pawel

2014-02-01

We study a biologically motivated model of overdamped, autochemotactic Brownian agents with concentration-dependent chemotactic sensitivity. The agents in our model move stochastically and produce a chemical ligand at their current position. The ligand concentration obeys a reaction-diffusion equation and acts as a chemoattractant for the agents, which bias their motion towards higher concentrations of the dynamically altered chemical field. We explore the impact of concentration-dependent response to chemoattractant gradients on large-scale pattern formation, by deriving a coarse-grained macroscopic description of the individual-based model, and compare the conditions for emergence of inhomogeneous solutions for different variants of the chemotactic sensitivity. We focus primarily on the so-called receptor-law sensitivity, which models a nonlinear decrease of chemotactic sensitivity with increasing ligand concentration. Our results reveal qualitative differences between the receptor law, the constant chemotactic response, and the so-called log law, with respect to stability of the homogeneous solution, as well as the emergence of different patterns (labyrinthine structures, clusters, and bubbles) via spinodal decomposition or nucleation. We discuss two limiting cases, where the model can be reduced to the dynamics of single species: (I) the agent density governed by a density-dependent effective diffusion coefficient and (II) the ligand field with an effective bistable, time-dependent reaction rate. In the end, we turn to single clusters of agents, studying domain growth and determining mean characteristics of the stationary inhomogeneous state. Analytical results are confirmed and extended by large-scale GPU simulations of the individual based model.

The copper complexation ability of a synthetic humic-like acid formed by an abiotic humification process and the effect of experimental factors on its copper complexation ability.

PubMed

Yang, Ting; Hodson, Mark E

2018-03-26

Humic acids have an important impact on the distribution, toxicity, and bioavailability of hazardous metals in the environment. In this study, a synthetic humic-like acid (SHLA) was prepared by an abiotic humification process using catechol and glycine as humic precursors and a MnO 2 catalyst. The effect of physico-chemical conditions (ionic strength from 0.01 to 0.5 M NaNO 3 , pH from 4 to 8, temperature from 25 to 45 °C, and humic acid concentration from 5 to 100 mg/L) on the complexation ability of SHLA for Cu 2+ were investigated. A commercial humic acid (CHA, CAS: 1415-93-6) from Sigma-Aldrich was also studied for comparison. The results showed that for pH 4 to 8, the conditional stability constants (log K) of SHLA and CHA were in the range 5.63-8.62 and 4.87-6.23, respectively, and complexation capacities (CC) were 1.34-2.61 and 1.42-2.31 mmol/g, respectively. The Cu complexation ability of SHLA was higher than that of the CHA due to its higher number of acidic functional groups (SHLA 19.19 mmol/g; CHA 3.87 mmol/g), extent of humification and aromaticity (AL/AR: 0.333 (SHLA); 1.554 (CHA)), and O-alkyl functional groups (SHLA 15.56%; CHA 3.45%). The log K and complexation efficiency (fraction of metal bound to SHLA) of SHLA were higher at higher pH, lower ionic strength, higher temperature, and higher SHLA concentration. Overall, SHLA was a good and promising complexation agent for copper in both soil washing of copper contaminated soil and the treatment of copper-containing wastewater.

Combination of FVIII and by-passing agent potentiates in vitro thrombin production in haemophilia A inhibitor plasma.

PubMed

Klintman, Jenny; Astermark, Jan; Berntorp, Erik

2010-11-01

The by-passing agents, recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (APCC), are important tools in the treatment of patients with haemophilia A and high-responding inhibitory antibodies. It has been observed clinically that in some patients undergoing immune tolerance induction the bleeding frequency decreases, hypothetically caused by a transient haemostatic effect of infused FVIII not measurable ex vivo. We evaluated how by-passing agents and factor VIII (FVIII) affect thrombin generation (TG) in vitro using plasma from 11 patients with severe haemophilia A and high titre inhibitors. Samples were spiked with combinations of APCC, rFVIIa and five different FVIII products. Combination of APCC and FVIII showed a synergistic effect in eliciting TG (P<0·005) for four FVIII products. When rFVIIa and FVIII were combined the interaction between the preparations was found to be additive. APCC and rFVIIa were then combined without FVIII, resulting in an additive effect on thrombin production. Each product separately increased TG above baseline. In conclusion, the amount of thrombin formed in vitro by adding a by-passing agent, was higher in the presence of FVIII. Our findings support the use of FVIII in by-passing therapy to optimize the haemostatic effect. © 2010 Blackwell Publishing Ltd.

Spectrophotometric studies on the complexation equilibria of Ni and Pb with 2-carboxy-2-hydroxy-5'-sulfo-formazylbenzene. Simultaneous determination of trace amounts of Ni and Pb.

PubMed

Hashem, Elham Y; Abu-Bakr, Mohamed S; Hussain, Sawsan M

2004-01-01

Spectrophotometric studies have been made to investigate the reaction of Nickel and Lead with 2-carboxy-2'-hydroxy-5'-sulfoformazyl-benzene (zincon) in 50%(v/v) ethanol-water at 25 degrees C and an ionic strength of 0.1 M NaClO4. A complete picture of the complexation equilibria in the pH range (4.2-12.0) for nickel and (1.9-11.5) for lead are presented. Simple, rapid, selective and sensitive methods for the spectro-photometric determination of nickel and lead has been developed based on the color reaction of their complexes with zincon. The methods allow the determination of 4.69 microg mL(-1) of nickel at pH = 6.3 (lambdamax = 665 nm) and 10.3 microg ml(-1) of lead at pH = 5.6 (lambdamax = 610 nm). The apparent molar absorptivities were epsilon = 1.3 x 10(4) L mol(-1) cm(-1) for nickel and epsilon = 0.6 x 10(4) L mol(-1) cm(-1) for lead. The interference of a large number of foreign ions and complexing agents has been studied. Thiosulphate, as masking agent allows the simultaneous determination of nickel and lead in the presence of high concentrations of copper. Ascorbic acid, sodium cyanide and or sodium fluoride provide the elimination of many other interferences. The methods have been applied successfully to the simultaneous determination of nickel and lead in an aluminium and non-ferrous alloy.

Novel Metals and Metal Complexes as Platforms for Cancer Therapy

PubMed Central

Frezza, Michael; Hindo, Sarmad; Chen, Di; Davenport, Andrew; Schmitt, Sara; Tomco, Dajena; Dou, Q. Ping

2013-01-01

Metals are essential cellular components selected by nature to function in several indispensable biochemical processes for living organisms. Metals are endowed with unique characteristics that include redox activity, variable coordination modes, and reactivity towards organic substrates. Due to their reactivity, metals are tightly regulated under normal conditions and aberrant metal ion concentrations are associated with various pathological disorders, including cancer. For these reasons, coordination complexes, either as drugs or prodrugs, become very attractive probes as potential anticancer agents. The use of metals and their salts for medicinal purposes, from iatrochemistry to modern day, has been present throughout human history. The discovery of cisplatin, cis-[PtII(NH3)2Cl2], was a defining moment which triggered the interest in platinum(II)- and other metal-containing complexes as potential novel anticancer drugs. Other interests in this field address concerns for uptake, toxicity, and resistance to metallodrugs. This review article highlights selected metals that have gained considerable interest in both the development and the treatment of cancer. For example, copper is enriched in various human cancer tissues and is a co-factor essential for tumor angiogenesis processes. However the use of copper-binding ligands to target tumor copper could provide a novel strategy for cancer selective treatment. The use of nonessential metals as probes to target molecular pathways as anticancer agents is also emphasized. Finally, based on the interface between molecular biology and bioinorganic chemistry the design of coordination complexes for cancer treatment is reviewed and design strategies and mechanisms of action are discussed. PMID:20337575

Bismuth generator method

DOEpatents

Bray, Lane Allan; DesChane, Jaquetta R.

1998-01-01

A method for separating .sup.213 Bi from a solution of radionuclides wherein the solution contains a concentration of the chloride ions and hydrogen ions adjusted to allow the formation of a chloride complex. The solution is then brought into contact with an anion exchange resin, whereupon .sup.213 Bi is absorbed from the solution and adhered onto the anion exchange resin in the chloride complex. Other non-absorbing radionuclides such as .sup.225 Ra, .sup.225 Ac, and .sup.221 Fr, along with HCl are removed from the anion exchange resin with a scrub solution. The .sup.213 Bi is removed from the anion exchange resin by washing the anion exchange resin with a stripping solution free of chloride ions and with a reduced hydrogen ion concentration which breaks the chloride anionic complex, releasing the .sup.213 Bi as a cation. In a preferred embodiment of the present invention, the anion exchange resin is provided as a thin membrane, allowing for extremely rapid adherence and stripping of the .sup.213 Bi. A preferred stripping solution for purification of .sup.213 Bi for use in medical applications includes sodium acetate, pH 5.5. A protein conjugated with bifunctional chelating agents in vivo with the NaOAc, to receive the .sup.213 Bi as it is being released from the anion exchange resin.

Bismuth generator method

DOEpatents

Bray, L.A.; DesChane, J.R.

1998-05-05

A method is described for separating {sup 213}Bi from a solution of radionuclides wherein the solution contains a concentration of the chloride ions and hydrogen ions adjusted to allow the formation of a chloride complex. The solution is then brought into contact with an anion exchange resin, whereupon {sup 213}Bi is absorbed from the solution and adhered onto the anion exchange resin in the chloride complex. Other non-absorbing radionuclides such as {sup 225}Ra, {sup 225}Ac, and {sup 221}Fr, along with HCl are removed from the anion exchange resin with a scrub solution. The {sup 213}Bi is removed from the anion exchange resin by washing the anion exchange resin with a stripping solution free of chloride ions and with a reduced hydrogen ion concentration which breaks the chloride anionic complex, releasing the {sup 213}Bi as a cation. In a preferred embodiment of the present invention, the anion exchange resin is provided as a thin membrane, allowing for extremely rapid adherence and stripping of the {sup 213}Bi. A preferred stripping solution for purification of {sup 213}Bi for use in medical applications includes sodium acetate, pH 5.5. A protein conjugated with bifunctional chelating agents in vivo with the NaOAc receives the {sup 213}Bi as it is being released from the anion exchange resin. 10 figs.

Optical Properties of Synthesized Nanoparticles ZnS Using Methacrylic Acid as the Capping Agent

NASA Astrophysics Data System (ADS)

Nazerdeylami, Somayeh; Saievar Iranizad, Esmaiel; Molaei, Mehdi

Optical analysis (UV-vis spectroscopy) of solution of ZnS nanoparticles prepared at room temperature by a chemical capping method using methacrylic acid (MAA) capping agent at concentration of 0.05, 0.2, 0.5 and 1.17 molar is investigated. The spectroscopy results indicate increasing of band gap of ZnS through increasing concentration of the methacrylic acid as capping agent in the solution. According to the relation of Effective Mass Approximation, it is concluded that the size of nanoparticles decreased with the increasing concentration of the capping agent in the tested solutions. The size of the particles is found to be in 1.77-2.05 nm range.

Semiempirical Quantum Chemistry Model for the Lanthanides: RM1 (Recife Model 1) Parameters for Dysprosium, Holmium and Erbium

PubMed Central

Filho, Manoel A. M.; Dutra, José Diogo L.; Rocha, Gerd B.; Simas, Alfredo M.; Freire, Ricardo O.

2014-01-01

Complexes of dysprosium, holmium, and erbium find many applications as single-molecule magnets, as contrast agents for magnetic resonance imaging, as anti-cancer agents, in optical telecommunications, etc. Therefore, the development of tools that can be proven helpful to complex design is presently an active area of research. In this article, we advance a major improvement to the semiempirical description of lanthanide complexes: the Recife Model 1, RM1, model for the lanthanides, parameterized for the trications of Dy, Ho, and Er. By representing such lanthanide in the RM1 calculation as a three-electron atom with a set of 5 d, 6 s, and 6 p semiempirical orbitals, the accuracy of the previous sparkle models, mainly concentrated on lanthanide-oxygen and lanthanide-nitrogen distances, is extended to other types of bonds in the trication complexes’ coordination polyhedra, such as lanthanide-carbon, lanthanide-chlorine, etc. This is even more important as, for example, lanthanide-carbon atom distances in the coordination polyhedra of the complexes comprise about 30% of all distances for all complexes of Dy, Ho, and Er considered. Our results indicate that the average unsigned mean error for the lanthanide-carbon distances dropped from an average of 0.30 Å, for the sparkle models, to 0.04 Å for the RM1 model for the lanthanides; for a total of 509 such distances for the set of all Dy, Ho, and Er complexes considered. A similar behavior took place for the other distances as well, such as lanthanide-chlorine, lanthanide-bromine, lanthanide, phosphorus and lanthanide-sulfur. Thus, the RM1 model for the lanthanides, being advanced in this article, broadens the range of application of semiempirical models to lanthanide complexes by including comprehensively many other types of bonds not adequately described by the previous models. PMID:24497945

Devices, systems, and methods for conducting sandwich assays using sedimentation

DOEpatents

Schaff, Ulrich Y; Sommer, Gregory J; Singh, Anup K; Hatch, Anson V

2015-02-03

Embodiments of the present invention are directed toward devices, systems, and method for conducting sandwich assays using sedimentation. In one example, a method includes generating complexes on a plurality of beads in a fluid sample, individual ones of the complexes comprising a capture agent, a target analyte, and a labeling agent. The plurality of beads including the complexes may be transported through a density media, wherein the density media has a density lower than a density of the beads and higher than a density of the fluid sample, and wherein the transporting occurs, at least in part, by sedimentation. Signal may be detected from the labeling agents of the complexes.

Pharmacokinetic and in vivo evaluation of a self-assembled gadolinium(III)-iron(II) contrast agent with high relaxivity.

PubMed

Parac-Vogt, Tatjana N; Vander Elst, Luce; Kimpe, Kristof; Laurent, Sophie; Burtéa, Carmen; Chen, Feng; Van Deun, Rik; Ni, Yicheng; Muller, Robert N; Binnemans, Koen

2006-01-01

A high-molecular weight tetrametallic supramolecular complex [(Ln-DTPA-phen)3Fe]- (Ln = Gd, Eu, La) has been obtained upon self-assembly around one iron(II) ion of three 1,10-phenantroline-based molecules substituted in 5'-position with the polyaminocarboxylate diethylenetriamine-N,N,N',N',N'-pentaacetate, DTPA-phen(4-). The ICP-MS measurements indicated that the lanthanide:iron ratio is 3:1. Photoluminescence spectra of [Eu-DTPA-phen](-) and of [(Eu-DTPA-phen)3Fe]- are nearly identical, implying that the first coordination sphere of the lanthanide(III) ion has not been changed upon coordination of phenantroline unit to iron(II) ion. NMRD measurements revealed that at 20 MHz and 310 K the relaxivity of the [(Gd-DTPA-phen)3Fe]- is equal to 9.5 +/- 0.3 s(-1) mM(-1) of Gd (28.5 s(-1) per millimole per liter of complex) which is significantly higher than that for Gd-DTPA (3.9 s(-1) mM(-1)). The pharmacokinetic parameters of [(Gd-DTPA-phen)3Fe]- in rats indicate that the elimination of [(Gd-DTPA-phen)3Fe]- is significantly slower than that of Gd-DTPA and is correlated with a reduced volume of distribution. The low volume of distribution and the longer elimination time (T(e1/2)) suggest that the agent is confined to the blood compartment, so it could have an important potential as a blood pool contrast agent. The biodistribution profile of [(Gd-DTPA-phen)3Fe]- 2 h after injection indicates significantly higher concentrations of [(Gd-DTPA-phen)3Fe]- as compared with Gd-DTPA in kidney, liver, lungs, heart and spleen. The images obtained on rats by MR angiography show the enhancement of the abdominal blood vessels. The signal intensity reaches a maximum of 55% at 7 min post-contrast and remains around 25% after 90 min. MRI-histomorphological correlation studies of [Gd-DTPA-phen]- and [(Gd-DTPA-phen)3Fe]- showed that both agents displayed potent contrast enhancement in organs including the liver. The necrosis avidity tests indicated that, in contrast to the [Gd-DTPA-phen](-) precursor complex, the supramolecular complex [(Gd-DTPA-phen)3Fe]- exhibits necrosis avidity. Copyright 2006 John Wiley & Sons, Ltd.

Citric-acid preacidification enhanced electrokinetic remediation for removal of chromium from chromium-residue-contaminated soil.

PubMed

Meng, Fansheng; Xue, Hao; Wang, Yeyao; Zheng, Binghui; Wang, Juling

2018-02-01

Electrokinetic experiments were conducted on chromium-residue-contaminated soils collected from a chemical plant in China. Acidification-electrokinetic remediation technology was proposed in order to solve the problem of removing inefficient with ordinary electrokinetic. The results showed that electrokinetic remediation removal efficiency of chromium from chromium-contaminated soil was significantly enhanced with acidizing pretreatment. The total chromium [Cr(T)] and hexavalent chromium [Cr(VI)] removal rate of the group acidized by citric acid (0.9 mol/L) for 5 days was increased from 6.23% and 19.01% in the acid-free experiments to 26.97% and 77.66% in the acidification-treated experiments, respectively. In addition, part of chromium with the state of carbonate-combined will be converted into water-soluble state through acidification to improve the removal efficiency. Within the appropriate concentration range, the higher concentration of acid was, the more chromium was released. So the removal efficiency of chromium depended on the acid concentration. The citric acid is also a kind of complexing agent, which produced complexation with Cr that was released by the electrokinetic treatment and then enhanced the removal efficiency. The major speciation of chromium that was removed from soils by acidification-electrokinetics remediation was acid-soluble speciation, revivification speciation and oxidation speciation, which reduced biological availability of chromium.

Monoclonal antibody to trivalent chromium chelate complex and its application to measurement of the total chromium concentration.

PubMed

Sasaki, Kazuhiro; Oguma, Shinichi; Namiki, Yukie; Ohmura, Naoya

2009-05-15

Isothiocyanobenzyl group-appended ethylenediamine tetraacetic acid (EDTA) was used to covalently couple Cr(III) x EDTA to keyhole limpet hemocyanin for use as an immunogen. An obtained monoclonal antibody (RD3G4) bound to Cr(III) x EDTA with an equilibrium dissociation constant (K(d)) of 9.7 nM, which was 100-fold tighter than the K(d)s for the other tested EDTA-metal complex. In particular, there was an over 2000-fold affinity difference between Cr(III) x EDTA and Fe(III) x EDTA, although the ion radius of trivalent chromium (0.76 A) was quite close to that of ferric ion (0.79 A). Hexavalent chromium could be detected by the antibody after being reduced into trivalent form. An immunoassay format showed an IC50 of 87 nM for hexavalent chromium, with a detection limit of 30 nM (1.6 microg/L). Therefore, the addition of reducing agents to the mixture of tri- and hexavalent chromium allows determination of the total chromium concentration by the immunoassay. Hexavalent chromium could be isolated from trivalent chromium by an anion-exchange column, and thus, the concentration of hexavalent chromium in tri- and hexa- mixture can also be estimated by the immunoassay.

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

PubMed

Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

2016-01-01

Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the concentration of microbubbles in case stable cavitation is predominant.

Early transcriptomic response to Fe supply in Fe-deficient tomato plants is strongly influenced by the nature of the chelating agent.

PubMed

Zamboni, Anita; Zanin, Laura; Tomasi, Nicola; Avesani, Linda; Pinton, Roberto; Varanini, Zeno; Cesco, Stefano

2016-01-07

It is well known that in the rhizosphere soluble Fe sources available for plants are mainly represented by a mixture of complexes between the micronutrient and organic ligands such as carboxylates and phytosiderophores (PS) released by roots, as well as fractions of humified organic matter. The use by roots of these three natural Fe sources (Fe-citrate, Fe-PS and Fe complexed to water-extractable humic substances, Fe-WEHS) have been already studied at physiological level but the knowledge about the transcriptomic aspects is still lacking. The (59)Fe concentration recorded after 24 h in tissues of tomato Fe-deficient plants supplied with (59)Fe complexed to WEHS reached values about 2 times higher than those measured in response to the supply with Fe-citrate and Fe-PS. However, after 1 h no differences among the three Fe-chelates were observed considering the (59)Fe concentration and the root Fe(III) reduction activity. A large-scale transcriptional analysis of root tissue after 1 h of Fe supply showed that Fe-WEHS modulated only two transcripts leaving the transcriptome substantially identical to Fe-deficient plants. On the other hand, Fe-citrate and Fe-PS affected 728 and 408 transcripts, respectively, having 289 a similar transcriptional behaviour in response to both Fe sources. The root transcriptional response to the Fe supply depends on the nature of chelating agents (WEHS, citrate and PS). The supply of Fe-citrate and Fe-PS showed not only a fast back regulation of molecular mechanisms modulated by Fe deficiency but also specific responses due to the uptake of the chelating molecule. Plants fed with Fe-WEHS did not show relevant changes in the root transcriptome with respect to the Fe-deficient plants, indicating that roots did not sense the restored cellular Fe accumulation.

Bimodal MR-PET agent for quantitative pH imaging

PubMed Central

Frullano, Luca; Catana, Ciprian; Benner, Thomas; Sherry, A. Dean; Caravan, Peter

2010-01-01

Activatable or “smart” magnetic resonance contrast agents have relaxivities that depend on environmental factors such as pH or enzymatic activity, but the MR signal depends on relaxivity and agent concentration – two unknowns. A bimodal approach, incorporating a positron emitter, solves this problem. Simultaneous positron emission tomography (PET) and MR imaging with the biomodal, pH-responsive MR-PET agent GdDOTA-4AMP-F allows direct determination of both concentration (PET) and T1 (MRI), and hence pH. PMID:20191650

Selective determination of heavy metals (Cd, Pb, Cr) speciation forms from hortic anthrosols

NASA Astrophysics Data System (ADS)

Bulgariu, Dumitru; Bulgariu, Laura; Filipov, Feodor; Astefanei, Dan; Stoleru, Vasile

2010-05-01

In soils from glass houses, the speciation and inter-phases distribution processes of heavy metals have a particular dynamic, different in comparison with those from non-protected soils. The predominant distribution forms of heavy metals in such soils types are: complexes with low mass organic molecules, organic-mineral complexes, complexes with inorganic ligands (hydroxide-complexes, carbonate-complexes, sulphate-complexes, etc.) and basic salts. All of these have high stabilities in conditions of soils from glass houses, and in consequence, the separation and determination of speciation forms (which is directly connected with biodisponibility of heavy metals) by usual methods id very difficult and has a high uncertain degree. In this study is presented an original method for the selective separation and differentiation of speciation forms of heavy metals from glass houses soils, which is based by the combination of solid-liquid sequential extraction (SPE) with the extraction in aqueous polymer-inorganic salt two-phase systems (ABS). The soil samples used for this study have been sampled from three different locations (glass houses from Iasi, Barlad and Bacau - Romania) where the vegetables cultivation have been performed by three different technologies. In this way was estimated the applicability and the analytical limits of method proposed by as, in function of the chemical-mineralogical and physical-chemical characteristics of soils. As heavy metals have been studied cadmium, lead and chromium, all being known for their high toxicity. The procedure used for the selective separation and differentiation of speciation forms of heavy metals from glass houses soils has two main steps: (i) non-destructive separation of chemical-mineralogical associations and aggregates from soils samples - for this the separation method with heavy liquids (bromophorme) and isodynamic magnetic method have been used; (ii) sequential extraction of heavy metals from soil fractions separated in the first step, by using combined SPE-ABS procedure. For the preparation of combined extraction systems was used polyethylene glycol (with different molecular mass: 2000, 4000 and 8000). As phase-forming inorganic salts and as selective extracting agents we have used different usual inorganic reagents. The type and concentration of phase-forming salts have been selected in function of, both nature of extracted heavy metals and chemical-mineralogical characteristics of soil samples. The experimental parameters investigated in this study are: molecular mass of polyethylene glycol and the concentration of polymeric solutions, nature and concentration of phase-forming salts, nature and concentration of extracting agents, pH in extraction system phase, type of extracted heavy metals, type of speciation forms of heavy metals and their concentrations. All these factors can influence significantly the efficiency and the selectivity of separation process. The experimental results have indicate that the combined SPE-ABS extraction systems have better separation efficiency, in comparison with traditional SPE systems and ca realized a accurate discrimination between speciation forms of heavy metals from soils. Under these conditions, the estimation of inter-phases distribution and biodisponibility of heavy metals has a high precision. On the other hand, when the combined SPE-ABS systems are used, the concomitant extraction of the elements from the same geochemical association with studied heavy metals (inevitable phenomena in case of separation by SPE procedures) is significant diminished. This increases the separation selectivity and facilitated the more accurate determination of speciation forms concentration. By adequate selection of extraction conditions can be realized the selective separation of organic-mineral complexes, which will permit to perform detailed studies about the structure and chemical composition of these. Acknowledgments The authors would like to acknowledge the financial support from Romanian Ministry of Education and Research (Project PNCDI 2-D5 no. 51045/07 and project PNCDI 2 - D5 no. 52-141 / 2008).

Selective Separation and Determination of Heavy Metals (Cd, Pb, Cr) Speciation Forms from Hortic Antrosols

NASA Astrophysics Data System (ADS)

Bulgariu, D.; Bulgariu, L.

2009-04-01

The speciation, inter-phases distribution and biodisponibility of heavy metals in soils represent one of main problem of environmental geochemistry and agro-chemistry. This problem is very important in case of hortic antrosols (soils from glasshouses) for the elimination of agricultural products (fruits, vegetables) contamination with heavy metals. In soils from glass houses, the speciation and inter-phases distribution processes of heavy metals have a particular dynamic, different in comparison with those from non-protected soils. The predominant distribution forms of heavy metals in such soils types are: complexes with low mass organic molecules, organic-mineral complexes, complexes with inorganic ligands (hydroxide-complexes, carbonate-complexes, sulphate-complexes, etc.) and basic salts. All of these have high stabilities in conditions of soils from glass houses, and in consequence, the separation and determination of speciation forms (which is directly connected with biodisponibility of heavy metals) by usual methods id very difficult and has a high uncertain degree. In this study is presented an original method for the selective separation and differentiation of speciation forms of heavy metals from glass houses soils, which is based by the combination of solid-liquid sequential extraction (SPE) with the extraction in aqueous polymer-inorganic salt two-phase systems (ABS). The soil samples used for this study have been sampled from three different locations (glass houses from Iasi, Barlad and Bacau - Romania) where the vegetables cultivation have bee performed by three different technologies. In this way was estimated the applicability and the analytical limits of method proposed by as, in function of the chemical-mineralogical and physical-chemical characteristics of soils. As heavy metals have been studied cadmium, lead and chromium, all being known for their high toxicity. The procedure used for the selective separation and differentiation of speciation forms of heavy metals from glass houses soils has two main steps: (i) non-destructive separation of chemical-mineralogical associations and aggregates from soils samples - for this the separation method with heavy liquids (bromophorme) and isodynamic magnetic method have been used; (ii) sequential extraction of heavy metals from soil fractions separated in the first step, by using combined SPE-ABS procedure. For the preparation of combined extraction systems was used polyethylene glycol (with different molecular mass: 2000, 4000 and 8000). As phase-forming inorganic salts and as selective extracting agents we have used different usual inorganic reagents. The type and concentration of phase-forming salts have been selected in function of, both nature of extracted heavy metals and chemical-mineralogical characteristics of soil samples. The experimental parameters investigated in this study are: molecular mass of polyethylene glycol and the concentration of polymeric solutions, nature and concentration of phase-forming salts, nature and concentration of extracting agents, pH in extraction system phase, type of extracted heavy metals, type of speciation forms of heavy metals and their concentrations. All these factors can influence significantly the efficiency and the selectivity of separation process. The experimental results have indicate that the combined SPE-ABS extraction systems have better separation efficiency, in comparison with traditional SPE systems and ca realized a accurate discrimination between speciation forms of heavy metals from soils. Under these conditions, the estimation of inter-phases distribution and biodisponibility of heavy metals has a high precision. On the other hand, when the combined SPE-ABS systems are used, the concomitant extraction of the elements from the same geochemical association with studied heavy metals (inevitable phenomena in case of separation by SPE procedures) is significant diminished. This increases the separation selectivity and facilitated the more accurate determination of speciation forms concentration. By adequate selection of extraction conditions can be realized the selective separation of organic-mineral complexes, which will permit to perform detailed studies about the structure and chemical composition of these. Acknowledgments The authors would like to acknowledge the financial support from Romanian Ministry of Education and Research (Project PNCDI 2-D5 no. 51045/07).

Regulated release of a novel non-viral gene delivery vector from electrospun coaxial fiber mesh scaffolds

NASA Astrophysics Data System (ADS)

Saraf, Anita

The development of novel strategies for tissue engineering entails the evolution of biopolymers into multifunctional constructs that can support the proliferation of cells and stimulate their differentiation into functional tissues. With that in mind, biocompatible polymers were fabricated into a novel gene delivery agent as well as three dimensional scaffolds that act as reservoirs and controlled release constructs. To fabricate a novel gene delivery agent a commercially available cationic polymer, poly(ethylenimine), PEI, was chemically conjugated to a ubiquitous glycosaminoglycan, hyaluronic acid (HA). The novel polymer, PEI-HA, had significantly reduced toxicity and improved transfection efficiency with multipotent human mesenchymal stem cells. This transfection efficiency could further be modulated by changing the concentration of sodium chloride and temperature used to assemble PEI-HA/DNA complexes. To facilitate the regulated delivery of these complexes in the context of tissue engineering, an emerging technology for scaffold fabrication, coaxial electrospinning was adapted to include PEI-HA and plasmid DNA within the scaffold fibers. Initially, a factorial design was employed to assess the influence of processing parameters in the absence of gene delivery vectors and plasmids. The study elucidated the role of sheath polymer concentration and core polymer concentration and molecular weight and the presence of sodium chloride on fiber diameters and morphologies. Subsequently, PEI-HA and plasmid DNA were entrapped within the sheath and core compartments of these fibers and the influence of processing parameters was assessed in the context of fiber diameter, release kinetics and transfection efficiency over a period of 60 days. The release of PEI-HA was found to be dependent upon the loading dose of the vector and plasmid. However, the transfection efficiency correlated to the core polymer properties, concentration and molecular weight. The processing parameters could modulate cell transfection for up to 21 days and continue to transfect cells for up to 60 days. Thus, scaffolds with tunable release kinetics and transfection efficiencies can be fabricated using coaxial electrospinning, which can further be used for tissue engineering and gene delivery applications.

Multi-agent based control of large-scale complex systems employing distributed dynamic inference engine

NASA Astrophysics Data System (ADS)

Zhang, Daili

Increasing societal demand for automation has led to considerable efforts to control large-scale complex systems, especially in the area of autonomous intelligent control methods. The control system of a large-scale complex system needs to satisfy four system level requirements: robustness, flexibility, reusability, and scalability. Corresponding to the four system level requirements, there arise four major challenges. First, it is difficult to get accurate and complete information. Second, the system may be physically highly distributed. Third, the system evolves very quickly. Fourth, emergent global behaviors of the system can be caused by small disturbances at the component level. The Multi-Agent Based Control (MABC) method as an implementation of distributed intelligent control has been the focus of research since the 1970s, in an effort to solve the above-mentioned problems in controlling large-scale complex systems. However, to the author's best knowledge, all MABC systems for large-scale complex systems with significant uncertainties are problem-specific and thus difficult to extend to other domains or larger systems. This situation is partly due to the control architecture of multiple agents being determined by agent to agent coupling and interaction mechanisms. Therefore, the research objective of this dissertation is to develop a comprehensive, generalized framework for the control system design of general large-scale complex systems with significant uncertainties, with the focus on distributed control architecture design and distributed inference engine design. A Hybrid Multi-Agent Based Control (HyMABC) architecture is proposed by combining hierarchical control architecture and module control architecture with logical replication rings. First, it decomposes a complex system hierarchically; second, it combines the components in the same level as a module, and then designs common interfaces for all of the components in the same module; third, replications are made for critical agents and are organized into logical rings. This architecture maintains clear guidelines for complexity decomposition and also increases the robustness of the whole system. Multiple Sectioned Dynamic Bayesian Networks (MSDBNs) as a distributed dynamic probabilistic inference engine, can be embedded into the control architecture to handle uncertainties of general large-scale complex systems. MSDBNs decomposes a large knowledge-based system into many agents. Each agent holds its partial perspective of a large problem domain by representing its knowledge as a Dynamic Bayesian Network (DBN). Each agent accesses local evidence from its corresponding local sensors and communicates with other agents through finite message passing. If the distributed agents can be organized into a tree structure, satisfying the running intersection property and d-sep set requirements, globally consistent inferences are achievable in a distributed way. By using different frequencies for local DBN agent belief updating and global system belief updating, it balances the communication cost with the global consistency of inferences. In this dissertation, a fully factorized Boyen-Koller (BK) approximation algorithm is used for local DBN agent belief updating, and the static Junction Forest Linkage Tree (JFLT) algorithm is used for global system belief updating. MSDBNs assume a static structure and a stable communication network for the whole system. However, for a real system, sub-Bayesian networks as nodes could be lost, and the communication network could be shut down due to partial damage in the system. Therefore, on-line and automatic MSDBNs structure formation is necessary for making robust state estimations and increasing survivability of the whole system. A Distributed Spanning Tree Optimization (DSTO) algorithm, a Distributed D-Sep Set Satisfaction (DDSSS) algorithm, and a Distributed Running Intersection Satisfaction (DRIS) algorithm are proposed in this dissertation. Combining these three distributed algorithms and a Distributed Belief Propagation (DBP) algorithm in MSDBNs makes state estimations robust to partial damage in the whole system. Combining the distributed control architecture design and the distributed inference engine design leads to a process of control system design for a general large-scale complex system. As applications of the proposed methodology, the control system design of a simplified ship chilled water system and a notional ship chilled water system have been demonstrated step by step. Simulation results not only show that the proposed methodology gives a clear guideline for control system design for general large-scale complex systems with dynamic and uncertain environment, but also indicate that the combination of MSDBNs and HyMABC can provide excellent performance for controlling general large-scale complex systems.

The Pathophysiology and Clinical Aspects of Hypercalcemic Disorders

PubMed Central

Lee, David B. N.; Zawada, Edward T.; Kleeman, Charles R.

1978-01-01

For the purposes of this review, the vast and increasingly complex subject of hypercalcemic disorders can be broken down into the following categories: (1) Physiochemical state of calcium in circulation. (2) Pathophysiological basis of hypercalcemia. (3) Causes of hypercalcemia encountered in clinical practice: causes indicated by experience at the University of California, Los Angeles; neoplasia; hyperparathyroidism; nonparathyroid endocrinopathies; pharmacological agents; possible increased sensitivity to vitamin D; miscellaneous causes. (4) Clinical manifestations and diagnostic considerations of hypercalcemic disorders. (5) The management of hypercalcemic disorders: general measures; measures for lowering serum calcium concentration; measures for correcting primary causes—the management of asymptomatic hyperparathyroidism. PMID:362722

Effect of Different Silage Storing Conditions on the Oxygen Concentration in the Silo and Fermentation Quality of Rice.

PubMed

Uegaki, Ryuichi; Kawano, Kazuo; Ohsawa, Ryo; Kimura, Toshiyuki; Yamamura, Kohji

2017-06-21

We investigated the effects of different silage storing conditions on the oxygen concentration in the silo and fermentation quality of rice (Oryza sativa L.). Forage rice was ensiled in bottles (with or without space at the bottlemouth, with solid or pinhole cap, and with oxygen scavenger, ethanol transpiration agent, oxygen scavenger and ethanol transpiration agent, or no adjuvant) and stored for 57 days. The oxygen concentration decreased with the addition of the oxygen scavenger and increased with that of the ethanol transpiration agent. The oxygen scavenger facilitated silage fermentation and fungus generation, whereas the ethanol transpiration agent suppressed silage fermentation and fungus generation. However, the combined use of the oxygen scavenger and ethanol transpiration agent facilitated silage fermentation and also suppressed fungus generation. Overall, this study revealed the negative effects of oxygen on the internal silo and the positive effects of the combined use of the oxygen scavenger and ethanol transpiration agent on silage fermentation quality.

Formalizing the role of agent-based modeling in causal inference and epidemiology.

PubMed

Marshall, Brandon D L; Galea, Sandro

2015-01-15

Calls for the adoption of complex systems approaches, including agent-based modeling, in the field of epidemiology have largely centered on the potential for such methods to examine complex disease etiologies, which are characterized by feedback behavior, interference, threshold dynamics, and multiple interacting causal effects. However, considerable theoretical and practical issues impede the capacity of agent-based methods to examine and evaluate causal effects and thus illuminate new areas for intervention. We build on this work by describing how agent-based models can be used to simulate counterfactual outcomes in the presence of complexity. We show that these models are of particular utility when the hypothesized causal mechanisms exhibit a high degree of interdependence between multiple causal effects and when interference (i.e., one person's exposure affects the outcome of others) is present and of intrinsic scientific interest. Although not without challenges, agent-based modeling (and complex systems methods broadly) represent a promising novel approach to identify and evaluate complex causal effects, and they are thus well suited to complement other modern epidemiologic methods of etiologic inquiry. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fusing terrain and goals: agent control in urban environments

NASA Astrophysics Data System (ADS)

Kaptan, Varol; Gelenbe, Erol

2006-04-01

The changing face of contemporary military conflicts has forced a major shift of focus in tactical planning and evaluation from the classical Cold War battlefield to an asymmetric guerrilla-type warfare in densely populated urban areas. The new arena of conflict presents unique operational difficulties due to factors like complex mobility restrictions and the necessity to preserve civilian lives and infrastructure. In this paper we present a novel method for autonomous agent control in an urban environment. Our approach is based on fusing terrain information and agent goals for the purpose of transforming the problem of navigation in a complex environment with many obstacles into the easier problem of navigation in a virtual obstacle-free space. The main advantage of our approach is its ability to act as an adapter layer for a number of efficient agent control techniques which normally show poor performance when applied to an environment with many complex obstacles. Because of the very low computational and space complexity at runtime, our method is also particularly well suited for simulation or control of a huge number of agents (military as well as civilian) in a complex urban environment where traditional path-planning may be too expensive or where a just-in-time decision with hard real-time constraints is required.

NGF-conjugated iron oxide nanoparticles promote differentiation and outgrowth of PC12 cells

NASA Astrophysics Data System (ADS)

Marcus, M.; Skaat, H.; Alon, N.; Margel, S.; Shefi, O.

2014-12-01

The search for regenerative agents that promote neuronal differentiation and repair is of great importance. Nerve growth factor (NGF) which is an essential contributor to neuronal differentiation has shown high pharmacological potential for the treatment of central neurodegenerative diseases such as Alzheimer's and Parkinson's. However, growth factors undergo rapid degradation, leading to a short biological half-life. In our study, we describe a new nano-based approach to enhance the NGF activity resulting in promoted neuronal differentiation. We covalently conjugated NGF to iron oxide nanoparticles (NGF-NPs) and studied the effect of the novel complex on the differentiation of PC12 cells. We found that the NGF-NP treatment, at the same concentration as free NGF, significantly promoted neurite outgrowth and increased the complexity of the neuronal branching trees. Examination of neuronal differentiation gene markers demonstrated higher levels of expression in PC12 cells treated with the conjugated factor. By manipulating the NGF specific receptor, TrkA, we have demonstrated that NGF-NPs induce cell differentiation via the regular pathway. Importantly, we have shown that NGF-NPs undergo slower degradation than free NGF, extending their half-life and increasing NGF availability. Even a low concentration of conjugated NGF treatment has led to an effective response. We propose the use of the NGF-NP complex which has magnetic characteristics, also as a useful method to enhance NGF efficiency and activity, thus, paving the way for substantial neuronal repair therapeutics.The search for regenerative agents that promote neuronal differentiation and repair is of great importance. Nerve growth factor (NGF) which is an essential contributor to neuronal differentiation has shown high pharmacological potential for the treatment of central neurodegenerative diseases such as Alzheimer's and Parkinson's. However, growth factors undergo rapid degradation, leading to a short biological half-life. In our study, we describe a new nano-based approach to enhance the NGF activity resulting in promoted neuronal differentiation. We covalently conjugated NGF to iron oxide nanoparticles (NGF-NPs) and studied the effect of the novel complex on the differentiation of PC12 cells. We found that the NGF-NP treatment, at the same concentration as free NGF, significantly promoted neurite outgrowth and increased the complexity of the neuronal branching trees. Examination of neuronal differentiation gene markers demonstrated higher levels of expression in PC12 cells treated with the conjugated factor. By manipulating the NGF specific receptor, TrkA, we have demonstrated that NGF-NPs induce cell differentiation via the regular pathway. Importantly, we have shown that NGF-NPs undergo slower degradation than free NGF, extending their half-life and increasing NGF availability. Even a low concentration of conjugated NGF treatment has led to an effective response. We propose the use of the NGF-NP complex which has magnetic characteristics, also as a useful method to enhance NGF efficiency and activity, thus, paving the way for substantial neuronal repair therapeutics. Electronic supplementary information (ESI) available: Conjugation ratio determination and supplementary figures. See DOI: 10.1039/c4nr05193a

Evaluation of the Sensititre MycoTB plate for susceptibility testing of the Mycobacterium tuberculosis complex against first- and second-line agents.

PubMed

Hall, Leslie; Jude, Kurt P; Clark, Shirley L; Dionne, Kim; Merson, Ryan; Boyer, Ana; Parrish, Nicole M; Wengenack, Nancy L

2012-11-01

The Sensititre MycoTB plate (TREK Diagnostic Systems, Cleveland, OH) uses a microtiter plate MIC format for susceptibility testing of Mycobacterium tuberculosis complex isolates against first- and second-line antituberculosis agents. Categorical agreement versus the agar proportion method for 122 M. tuberculosis complex isolates was 94% to 100%.

Enhancement of bioavailability of cinnarizine from its beta-cyclodextrin complex on oral administration with DL-phenylalanine as a competing agent.

PubMed

Tokumura, T; Nanba, M; Tsushima, Y; Tatsuishi, K; Kayano, M; Machida, Y; Nagai, T

1986-04-01

The present investigation is concerned with an improvement of the bioavailability of cinnarizine by administering its beta-cyclodextrin complex together with another compound which competes with the beta-cyclodextrin molecule in complex formation in aqueous solution (competing agent). The bioavailability of cinnarizine on oral administration of the cinnarizine-beta-cyclodextrin inclusion complex was enhanced by the simultaneous administration of DL-phenylalanine as a competing agent, e.g., the AUC was 1.9 and 2.7 times as large as those of the cinnarizine-beta-cyclodextrin complex alone and cinnarizine alone, respectively. The enhancement of AUC and Cmax completely depended on the dose of DL-phenylalanine. It was found from these results that DL-phenylalanine acted as a competing agent in the GI tract and the minimum effective dose required of DL-phenylalanine might be 1 g for 50 mg of cinnarizine in the cinnarizine-beta-cyclodextrin complex. Evaluating the competing effect of DL-phenylalanine in vitro using an absorption simulator, it was found that the decreased penetration rate of cinnarizine through the artificial lipid barrier with addition of beta-cyclodextrin was restored with the addition of DL-phenylalanine.

Toxin activity assays, devices, methods and systems therefor

DOEpatents

Koh, Chung-Yan; Schaff, Ulrich Y.; Sommer, Gregory Jon

2016-04-05

Embodiments of the present invention are directed toward devices, system and method for conducting toxin activity assay using sedimentation. The toxin activity assay may include generating complexes which bind to a plurality of beads in a fluid sample. The complexes may include a target toxin and a labeling agent, or may be generated due to presence of active target toxin and/or labeling agent designed to be incorporated into complexes responsive to the presence of target active toxin. The plurality of beads including the complexes may be transported through a density media, wherein the density media has a lower density than a density of the beads and higher than a density of the fluid sample, and wherein the transporting occurs, at least in part, by sedimentation. Signal may be detected from the labeling agents of the complexes.

Isobolographic Analysis of Pharmacodynamic Interactions between Antifungal Agents and Ciprofloxacin against Candida albicans and Aspergillus fumigatus▿

PubMed Central

Stergiopoulou, Theodouli; Meletiadis, Joseph; Sein, Tin; Papaioannidou, Paraskevi; Tsiouris, Ioannis; Roilides, Emmanuel; Walsh, Thomas J.

2008-01-01

Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Assessment of pharmacodynamic interactions between antifungal and antibacterial agents is complicated by the absence of a common antifungal end point for both agents. Ciprofloxacin has no intrinsic antifungal activity but may interact with antifungal agents, since it inhibits DNA gyrase (topoisomerase II), which is abundant in fungi. We therefore employed isobolographic analysis adapted to incorporate a nonactive agent in order to analyze the potential in vitro interaction between the fluoroquinolone ciprofloxacin and several representative antifungal agents against Candida albicans and Aspergillus fumigatus strains by using a microdilution checkerboard technique. In agreement with earlier in vitro studies, conventional fractional inhibitory concentration index analysis was unable to detect interactions between ciprofloxacin and antifungal agents. However, isobolographic analysis revealed significant pharmacodynamic interactions between antifungal agents and ciprofloxacin against C. albicans and A. fumigatus strains. Amphotericin B demonstrated concentration-dependent interactions for both species, with synergy (interaction indices, 0.14 to 0.81) observed at ciprofloxacin concentrations of <10.64 μg/ml. Synergy (interaction indices, 0.10 to 0.86) was also found for voriconazole and caspofungin against A. fumigatus. Isobolographic analysis may help to elucidate the pharmacodynamic interactions between antifungal and non-antifungal agents and to develop better management strategies against invasive candidiasis and aspergillosis. PMID:18299413

Management of Bleeding With Non-Vitamin K Antagonist Oral Anticoagulants in the Era of Specific Reversal Agents.

PubMed

Ruff, Christian T; Giugliano, Robert P; Antman, Elliott M

2016-07-19

Vitamin K antagonists are commonly used by clinicians to provide anticoagulation to patients who have or are at risk of having thrombotic events. In addition to familiarity with the dosing and monitoring of vitamin K antagonists, clinicians are accustomed to using vitamin K if there is a need to reverse the anticoagulant effect of vitamin K antagonists. There are now 4 new non-vitamin K antagonist oral anticoagulants (NOACs) that are attractive alternatives to vitamin K antagonists. Despite similar or lower rates of serious bleeding with NOACs in comparison with warfarin, there is a pressing need for strategies to manage bleeding when it does occur with NOACs and to reverse the pharmacological effect of these agents if needed. Important steps in minimizing bleeding risks with NOACs include dose adjustment of the agents in the setting of renal dysfunction and avoidance of the concomitant use of other antithrombotic agents if feasible. Laboratory measurement of the anticoagulant effect of NOACs is best accomplished with specialized assays, although some of the more widely available coagulation tests can provide information that is potentially useful to clinicians. Nonspecific hemostatic agents such as prothrombin complex concentrates and recombinant factor VIIa can be used to reverse the effect of NOACs. More specific reversing agents include the approved humanized monoclonal antibody fragment idarucizumab for reversing the effects of dabigatran, the investigational factor Xa decoy andexanet alfa, and the synthetic small molecule ciraparantag. Both andexanet and ciraparantag have been reported to reverse the effects of the anti-Xa NOACs (rivaroxaban, apixaban, and edoxaban), and a number of other anticoagulant agents in common clinical use, as well. © 2016 American Heart Association, Inc.

Formulation and performance test of palm-based foaming agent concentrate for fire extinguisher application

NASA Astrophysics Data System (ADS)

Rivai, M.; Hambali, E.; Suryani, A.; Fitria, R.; Firmansyah, S.; Pramuhadi, G.

2018-03-01

The utilization of foaming agent for fire extinguisher application improves the efficiency of water as a fire extinguishing agent, lowers surface tension, and acts as a foaming agent. The formed foam cools the fire down and covers the burned material to avoid it from further contact with oxygen which may reignite the fire. This study aimed to produce and assess the performance of foaming agent concentrate from palm oil as a fire extinguisher agent. In the performance test, measurements were taken on foam stability, foaming ability, surface tension, interfacial tension, viscosity, contact angle, density, and specific gravity. The formulation was conducted by using the best produced potassium palmitate, potassium methyl ester, and sodium lauric combined with diluents, chelating agent, and other additives at various composition comparisons. The produced foaming agent concentrate was found to be in a rather paste and liquid form with viscosity of 2.34 – 253 cP. It was also found that the resulted foaming agent concentrate dissolved in water at the concentration rate of 1% had a foam stability level of 30-91%, foaming ability of 288 – 503%, surface tension of 19.68 – 25.05 dyne/cm, interfacial tension of 0.54 – 4,20 dyne/cm, viscosity of 1.00 – 1.05 cP, contact angles of 53.75 – 63.79° at 0 minute and 11.84 – 22.42 ° at minute 10, density of 0.99586 – 0.99612 g/cm3, and a specific gravity of 1.00021 – 1.00046. Based on foam stability, foaming ability, and surface tension parameters, it was concluded that NF5 and NF17 were the best formulas.Compared to the other formulas, NF5 formula had the best droplet diameter (minimum 0.14 mm) and droplet density (maximum 3056 droplets/cm2).

Mitochondria are the primary target in the induction of apoptosis by chiral ruthenium(II) polypyridyl complexes in cancer cells.

PubMed

Wang, Jin-Quan; Zhang, Ping-Yu; Qian, Chen; Hou, Xiao-Juan; Ji, Liang-Nian; Chao, Hui

2014-03-01

A series of novel chiral ruthenium(II) polypyridyl complexes (Δ-Ru1, Λ-Ru1, Δ-Ru2, Λ-Ru2, Δ-Ru3, Λ-Ru3) were synthesized and evaluated to determine their antiproliferative activities. Colocalization, inductively coupled plasma mass spectrometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay studies showed that these ruthenium(II) complexes accumulated preferentially in the mitochondria and exhibited cytotoxicity against various cancer cells in vitro. The complex Δ-Ru1 is of particular interest because it was found to have half-maximal inhibitory concentrations comparable to those of cisplatin and better activity than cisplatin against a cisplatin-resistant cell line, A549-CP/R. Δ-Ru1 induced alterations in the mitochondrial membrane potential and triggered intrinsic mitochondria-mediated apoptosis in HeLa cells, which involved the regulation of Bcl-2 family members and the activation of caspases. Taken together, these data suggest that Δ-Ru1 may be a novel mitochondria-targeting anticancer agent.

Cloud point extraction: an alternative to traditional liquid-liquid extraction for lanthanides(III) separation.

PubMed

Favre-Réguillon, Alain; Draye, Micheline; Lebuzit, Gérard; Thomas, Sylvie; Foos, Jacques; Cote, Gérard; Guy, Alain

2004-06-17

Cloud point extraction (CPE) was used to extract and separate lanthanum(III) and gadolinium(III) nitrate from an aqueous solution. The methodology used is based on the formation of lanthanide(III)-8-hydroxyquinoline (8-HQ) complexes soluble in a micellar phase of non-ionic surfactant. The lanthanide(III) complexes are then extracted into the surfactant-rich phase at a temperature above the cloud point temperature (CPT). The structure of the non-ionic surfactant, and the chelating agent-metal molar ratio are identified as factors determining the extraction efficiency and selectivity. In an aqueous solution containing equimolar concentrations of La(III) and Gd(III), extraction efficiency for Gd(III) can reach 96% with a Gd(III)/La(III) selectivity higher than 30 using Triton X-114. Under those conditions, a Gd(III) decontamination factor of 50 is obtained.

Interaction and Communication of Agents in Networks and Language Complexity Estimates

NASA Technical Reports Server (NTRS)

Smid, Jan; Obitko, Marek; Fisher, David; Truszkowski, Walt

2004-01-01

Knowledge acquisition and sharing are arguably the most critical activities of communicating agents. We report about our on-going project featuring knowledge acquisition and sharing among communicating agents embedded in a network. The applications we target range from hardware robots to virtual entities such as internet agents. Agent experiments can be simulated using a convenient simulation language. We analyzed the complexity of communicating agent simulations using Java and Easel. Scenarios we have studied are listed below. The communication among agents can range from declarative queries to sub-natural language queries. 1) A set of agents monitoring an object are asked to build activity profiles based on exchanging elementary observations; 2) A set of car drivers form a line, where every car is following its predecessor. An unsafe distance cm create a strong wave in the line. Individual agents are asked to incorporate and apply directions how to avoid the wave. 3) A set of micro-vehicles form a grid and are asked to propagate information and concepts to a central server.

Short communication: The influence of solids concentration and bleaching agent on bleaching efficacy and flavor of sweet whey powder.

PubMed

Jervis, M G; Smith, T J; Drake, M A

2015-04-01

Recent studies have demonstrated the effect of bleaching conditions and bleaching agent on flavor and functional properties of whey protein ingredients. Solids concentration at bleaching significantly affected bleaching efficacy and flavor effects of different bleaching agents. It is not known if these parameters influence quality of sweet whey powder (SWP). The purpose of this study was to determine the effects of solids concentration and bleaching agent on the flavor and bleaching efficacy of SWP. Colored cheddar whey was manufactured, fat separated, and pasteurized. Subsequently, the whey (6.7% solids) was bleached, concentrated using reverse osmosis (RO) to 14% solids, and then spray dried, or whey was concentrated before bleaching and then spray dried. Bleaching treatments included a control (no bleaching, 50 °C, 60 min), hydrogen peroxide (HP; 250 mg/kg, 50 °C, 60 min), benzoyl peroxide (50 mg/kg, 50 °C, 60 min), lactoperoxidase (20 mg/kg of HP, 50 °C, 30 min), and external peroxidase (MaxiBright, DSM Food Specialties, Delft, the Netherlands; 2 dairy bleaching units/mL, 50 °C, 30 min). The experiment was repeated in triplicate. Sensory properties and volatile compounds of SWP were evaluated by a trained panel and gas chromatography-mass spectrometry, respectively. Bleaching efficacy (norbixin destruction) and benzoic acid were measured by HPLC. Differences in bleaching efficacy, sensory and volatile compound profiles, and benzoic acid were observed with different bleaching agents, consistent with previous studies. Solids concentration affected bleaching efficacy of HP, but not other bleaching agents. The SWP from whey bleached with HP or lactoperoxidase following RO had increased cardboard and fatty flavors and higher concentrations of lipid oxidation compounds compared with SWP from whey bleached before RO. The SWP bleached with benzoyl peroxide after RO contained less benzoic acid than SWP from whey bleached before RO. These results indicate that solids concentration at bleaching and bleaching agent affect quality of SWP. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Generalized paired-agent kinetic model for in vivo quantification of cancer cell-surface receptors under receptor saturation conditions

NASA Astrophysics Data System (ADS)

Sadeghipour, N.; Davis, S. C.; Tichauer, K. M.

2017-01-01

New precision medicine drugs oftentimes act through binding to specific cell-surface cancer receptors, and thus their efficacy is highly dependent on the availability of those receptors and the receptor concentration per cell. Paired-agent molecular imaging can provide quantitative information on receptor status in vivo, especially in tumor tissue; however, to date, published approaches to paired-agent quantitative imaging require that only ‘trace’ levels of imaging agent exist compared to receptor concentration. This strict requirement may limit applicability, particularly in drug binding studies, which seek to report on a biological effect in response to saturating receptors with a drug moiety. To extend the regime over which paired-agent imaging may be used, this work presents a generalized simplified reference tissue model (GSRTM) for paired-agent imaging developed to approximate receptor concentration in both non-receptor-saturated and receptor-saturated conditions. Extensive simulation studies show that tumor receptor concentration estimates recovered using the GSRTM are more accurate in receptor-saturation conditions than the standard simple reference tissue model (SRTM) (% error (mean  ±  sd): GSRTM 0  ±  1 and SRTM 50  ±  1) and match the SRTM accuracy in non-saturated conditions (% error (mean  ±  sd): GSRTM 5  ±  5 and SRTM 0  ±  5). To further test the approach, GSRTM-estimated receptor concentration was compared to SRTM-estimated values extracted from tumor xenograft in vivo mouse model data. The GSRTM estimates were observed to deviate from the SRTM in tumors with low receptor saturation (which are likely in a saturated regime). Finally, a general ‘rule-of-thumb’ algorithm is presented to estimate the expected level of receptor saturation that would be achieved in a given tissue provided dose and pharmacokinetic information about the drug or imaging agent being used, and physiological information about the tissue. These studies suggest that the GSRTM is necessary when receptor saturation exceeds 20% and highlight the potential for GSRTM to accurately measure receptor concentrations under saturation conditions, such as might be required during high dose drug studies, or for imaging applications where high concentrations of imaging agent are required to optimize signal-to-noise conditions. This model can also be applied to PET and SPECT imaging studies that tend to suffer from noisier data, but require one less parameter to fit if images are converted to imaging agent concentration (quantitative PET/SPECT).

The interaction of phytosiderophores with soil as a function of time

NASA Astrophysics Data System (ADS)

Schenkeveld, W. D. C.; Oburger, E.; Schindlegger, Y.; Regelsberger, A.; Hann, S.; Puschenreiter, M.; Kraemer, S. M.

2012-04-01

Graminaceous plant species (grasses) exude natural chelating agents, called phytosiderophores (PS) for the purpose of iron acquisition, in particular under conditions of iron deficiency stress. The biogeochemistry of phytosiderophores in the rhizosphere is still poorly understood. Processes like mobilization of iron or other metals by PS, and the degradation of the chelating agent were previously studied under conditions quite remote from those observed in the rhizosphere, e.g. in hydroponics systems or in soil suspensions with low soils to solution ratios. Such experimental conditions may lead to artifacts like for instance the depletion of available metal fractions. The aim of the present study is to contribute to a more accurate quantification of the source and sink terms determining PS concentrations in the rhizosphere. The mobilization of iron and other metals from two clay soils and two sandy soils by the PS deoxymugineic acid (DMA) was studied as a function of time in a batch experiment with a soil-solution ratio of 1. Both soils causing iron deficiency stress in plants and a reference soil not doing so were included. To examine the effect of ligand biodegradation on metal mobilization, treatments with and without sterilant (azide) were included. The fraction of added DMA mobilizing Fe ranged from 10 to 60% and correlates positively with Fe availability (DTPA-extractable Fe) and negatively with the clay content of the soils. In particular in soils of low Fe availability, Fe mobilization by DMA was severely compromised by mobilization of other metals including Cu, Zn, Ni and Co. The relative importance of Zn as competing cation decreases over time, while the importance of Cu increases. In the treatment without sterilant addition, metal-DMA complexes were removed from solution after 4 days in all soils; in the clay soils, Fe-DMA complexes were already removed before. The highest concentration of mobilized Fe did not depend on whether sterilant was added or not, except in one soil; this concentration was reached after 0.25 up to 8 hours. Also in treatments with sterilant addition, the FeDMA concentration eventually declined, but removal from solution was not complete when the experiment ended after one week. This indicates that besides biodegradation there are other processes significantly compromising the FeDMA concentration in the soil. In summary, these results emphasize the importance of the kinetics and thermodynamics of coupled rhizosphere processes for plant iron acquisition.

Functionalized Derivatives of Benzo-Crown Ethers. Part 4. Antifungal Macrocyclic Supramolecular Complexes of Transition Metal Ions Acting as Lanosterol-14-α-Demethylase Ihibitors

PubMed Central

Barboiu, Mihai; Scozzafava, Andrea; Guran, Cornelia; Diaconescu, Paula; Bojin, Mihaela; Iluc, Vlad; Cot, Louis

1999-01-01

Poly- and mononuclear metal complexes of 2,3,11,12-bis[4-(10-aminodecylcarbonyl)]benzo-18- crown-6 (L) and Cu(II); Ni(II); Co(II) and Cr(III) have been synthesized and characterized by standard physico-chemical procedures. In the newly prepared complexes the crown moiety oxygen atoms of the macrocyclic host did not generally interact with metal ions, whereas the two amino groups of the ligand always did. Several of the newly synthesized compounds act as effective antifungal agents against Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 0.3−0.5 μg/mL. The mechanism of antifungal action of these coordination compounds is probably connected to an inhibition of lanosterol-14-α-demethylase, a metallo-enzyme playing a key role in sterol biosynthesis in fungi, bacteria and eukariotes. PMID:18475888

Development of Orodispersible Tablets of Candesartan Cilexetil-β-cyclodextrin Complex

PubMed Central

Sravya, Maddukuri; Deveswaran, Rajamanickam; Bharath, Srinivasan; Basavaraj, Basappa Veerbadraiah; Madhavan, Varadharajan

2013-01-01

The aim of this study was to investigate the use of inclusion complexation technique employing β-cyclodextrin in improving the dissolution profile of candesartan cilexetil, a BCS class-II drug, and to formulate the inclusion complex into orodispersible tablets. The inclusion complexes were formed by physical mixing, kneading, coevaporation, and lyophilisation methods. Inclusion complexes were characterized by FTIR, DSC, XRD, NMR, and mass spectral studies. Inclusion complexes prepared using kneading, and lyophilisation techniques in the molar ratio 1 : 5 with β-cyclodextrin were used for formulating orodispersible tablets by direct compression with different superdisintegrants like croscarmellose sodium, crospovidone, sodium starch glycolate, and low substituted hydroxypropyl cellulose in varying concentrations. The directly compressible powder was evaluated for precompression parameters, and the prepared orodispersible tablets were evaluated for postcompression parameters. Drug-excipient compatibility studies showed no interaction, and characterization proved the formation of inclusion complex. In vitro disintegration time was found to be within 3 minutes, and all the formulations showed complete drug release of 100% within 20 minutes. The optimized formulation was found to be stable after 6 months and showed no significant change in drug content. This work proved β-cyclodextrins to be effective solubilizing agent in improving the solubility of poorly water soluble drugs. PMID:26555987

Recent patents therapeutic agents for cancer.

PubMed

Li, Xun; Xu, Wenfang

2006-06-01

Cancer is one of the most dreaded diseases with a complex pathogenesis, which threats human life greatly. Multidisciplinary scientific investigations are making best efforts to combat this disease and put to the identification of novel anticancer agents. Patent anticancer agents registered in China are therefore increasing dramatically during the past ten years, which will be reviewed briefly in this article. platinum complexes anthracycline analogs (including doxorubicin derivatives) quinoline analogs podophyllotoxins analogs taxane analogs camptothecin (CPT) analogs.

Low-temperature thermally regenerative electrochemical system

DOEpatents

Loutfy, R.O.; Brown, A.P.; Yao, N.P.

1982-04-21

A thermally regenerative electrochemical system is described including an electrochemical cell with two water-based electrolytes separated by an ion exchange membrane, at least one of the electrolytes containing a complexing agent and a salt of a multivalent metal whose respective order of potentials for a pair of its redox couples is reversible by a change in the amount of the ocmplexing agent in the electrolyte, the complexing agent being removable by distillation to cause the reversal.

Approach for Autonomous Control of Unmanned Aerial Vehicle Using Intelligent Agents for Knowledge Creation

NASA Technical Reports Server (NTRS)

Dufrene, Warren R., Jr.

2004-01-01

This paper describes the development of a planned approach for Autonomous operation of an Unmanned Aerial Vehicle (UAV). A Hybrid approach will seek to provide Knowledge Generation thru the application of Artificial Intelligence (AI) and Intelligent Agents (IA) for UAV control. The application of many different types of AI techniques for flight will be explored during this research effort. The research concentration will be directed to the application of different AI methods within the UAV arena. By evaluating AI approaches, which will include Expert Systems, Neural Networks, Intelligent Agents, Fuzzy Logic, and Complex Adaptive Systems, a new insight may be gained into the benefits of AI techniques applied to achieving true autonomous operation of these systems thus providing new intellectual merit to this research field. The major area of discussion will be limited to the UAV. The systems of interest include small aircraft, insects, and miniature aircraft. Although flight systems will be explored, the benefits should apply to many Unmanned Vehicles such as: Rovers, Ocean Explorers, Robots, and autonomous operation systems. The flight system will be broken down into control agents that will represent the intelligent agent approach used in AI. After the completion of a successful approach, a framework of applying a Security Overseer will be added in an attempt to address errors, emergencies, failures, damage, or over dynamic environment. The chosen control problem was the landing phase of UAV operation. The initial results from simulation in FlightGear are presented.

Relative diffusion of paramagnetic metal complexes of MRI contrast agents in an isotropic hydrogel medium.

PubMed

Weerakoon, Bimali Sanjeevani; Osuga, Toshiaki

2017-03-01

The observation of molecular diffusion by means of magnetic resonance imaging (MRI) is significant in the evaluation of the metabolic activity of living tissues. Series of MRI examinations were conducted on a diffusion model to study the behaviour of the diffusion process of different-molecular-weight (MW) paramagnetic MRI contrast agents in an isotropic agar hydrogel medium. The model consisted of a solidified 1 % agar gel with an initial concentration of 0.5 mmol/L contrast solution layered on top of the gel. The diffusion process was monitored at pre-determined time intervals of immediately, 1, 6, 9, 23, and 48 h after introduction of the contrast agents onto the agar gel with a T1-weighted spin-echo (SE) pulse sequence. Three types of paramagnetic contrast agents, Gd-DTPA with a MW of 547.57 g/mol, Prohance with a MW of 558.69 g/mol and MnCl 2 with a MW of 125.84 g/mol, resulted in an approximate average diffusional displacement ratio of 1:1:2 per hour, respectively, within 48 h of the experiment. Therefore, the results of this study supported the hypothesis that the rate of the diffusion process of MRI contrast agents in the agar hydrogel medium is inversely related to their MWs. However, more repetitions are necessary under various types of experimental conditions and also with various types of contrast media of different MWs for further confirmation and validation of these results.

Evaluating porewater polycyclic aromatic hydrocarbon-related toxicity at a contaminated sediment site using a spiked field-sediment approach.

PubMed

Hartzell, Sharon E; Unger, Michael A; Vadas, George G; Yonkos, Lance T

2018-03-01

Although the complexity of contaminant mixtures in sediments can confound the identification of causative agents of adverse biological response, understanding the contaminant(s) of primary concern at impacted sites is critical to sound environmental management and remediation. In the present study, a stock mixture of 18 polycyclic aromatic hydrocarbon (PAH) compounds was prepared to reflect the variety and relative proportions of PAHs measured in surface sediment samples collected from discrete areas of a historically contaminated industrial estuary. This site-specific PAH stock mixture was spiked into nontoxic in-system and out-of-system field-collected reference sediments in dilution series spanning the range of previously measured total PAH concentrations from the region. Spiked sediments were evaluated in 10-d Leptocheirus plumulosus tests to determine whether toxicity in laboratory-created PAH concentrations was similar to the toxicity found in field-collected samples with equivalent PAH concentrations. The results show that toxicity of contaminated sediments was not explained by PAH exposure, while indicating that toxicity in spiked in-system (fine grain, high total organic carbon [TOC]) and out-of-system (course grain, low TOC) sediments was better explained by porewater PAH concentrations, measured using an antibody-based biosensor that quantified 3- to 5-ring PAHs, than total sediment PAH concentrations. The study demonstrates the application of site-specific spiking experiments to evaluate sediment toxicity at sites with complex mixtures of multiple contaminant classes and the utility of the PAH biosensor for rapid sediment-independent porewater PAH analysis. Environ Toxicol Chem 2018;37:893-902. © 2017 SETAC. © 2017 SETAC.

A Combined Theoretical and Experimental Study for Silver Electroplating

PubMed Central

Liu, Anmin; Ren, Xuefeng; An, Maozhong; Zhang, Jinqiu; Yang, Peixia; Wang, Bo; Zhu, Yongming; Wang, Chong

2014-01-01

A novel method combined theoretical and experimental study for environmental friendly silver electroplating was introduced. Quantum chemical calculations and molecular dynamic (MD) simulations were employed for predicting the behaviour and function of the complexing agents. Electronic properties, orbital information, and single point energies of the 5,5-dimethylhydantoin (DMH), nicotinic acid (NA), as well as their silver(I)-complexes were provided by quantum chemical calculations based on density functional theory (DFT). Adsorption behaviors of the agents on copper and silver surfaces were investigated using MD simulations. Basing on the data of quantum chemical calculations and MD simulations, we believed that DMH and NA could be the promising complexing agents for silver electroplating. The experimental results, including of electrochemical measurement and silver electroplating, further confirmed the above prediction. This efficient and versatile method thus opens a new window to study or design complexing agents for generalized metal electroplating and will vigorously promote the level of this research region. PMID:24452389

Chlorhexidine: beta-cyclodextrin inhibits yeast growth by extraction of ergosterol.

PubMed

Teixeira, K I R; Araújo, P V; Sinisterra, R D; Cortés, M E

2012-04-01

Chlorhexidine (Cx) augmented with beta-cyclodextrin (β-cd) inclusion compounds, termed Cx:β-cd complexes, have been developed for use as antiseptic agents. The aim of this study was to examine the interactions of Cx:β-cd complexes, prepared at different molecular ratios, with sterol and yeast membranes. The Minimal Inhibitory Concentration (MIC) against the yeast Candida albicans (C.a.) was determined for each complex; the MICs were found to range from 0.5 to 2 μg/mL. To confirm the MIC data, quantitative analysis of viable cells was performed using trypan blue staining. Mechanistic characterization of the interactions that the Cx:β-cd complexes have with the yeast membrane and assessment of membrane morphology following exposure to Cx:β-cd complexes were performed using Sterol Quantification Method analysis (SQM) and scanning electron microscopy (SEM). SQM revealed that sterol extraction increased with increasing β-cd concentrations (1.71 ×10(3); 1.4 ×10(3); 3.45 ×10(3), and 3.74 ×10(3) CFU for 1:1, 1:2, 1:3, and 1:4, respectively), likely as a consequence of membrane ergosterol solubilization. SEM images demonstrated that cell membrane damage is a visible and significant mechanism that contributes to the antimicrobial effects of Cx:β-cd complexes. Cell disorganization increased significantly as the proportion of β-cyclodextrin present in the complex increased. Morphology of cells exposed to complexes with 1:3 and 1:4 molar ratios of Cx:β-cd were observed to have large aggregates mixed with yeast remains, representing more membrane disruption than that observed in cells treated with Cx alone. In conclusion, nanoaggregates of Cx:β-cd complexes block yeast growth via ergosterol extraction, permeabilizing the membrane by creating cluster-like structures within the cell membrane, possibly due to high amounts of hydrogen bonding.

Determination of trace iron in the boiler water used in power generation plants by solid-phase spectrophotometry.

PubMed

Sarenqiqige; Maeda, Akihiro; Yoshimura, Kazuhisa

2014-01-01

A sensitive, simple and low-cost determination method for the total iron concentration in boiler water systems of power generation plants was developed by solid phase spectrometry (SPS) using 2,4,6-tris(2-pyridyl)-1,3,5-triazine (TPTZ) as a coloring agent. The reagents and 0.08 cm(3) of a cation exchanger were added to a 50-cm(3) boiler water sample, then mixed for 30 min to adsorb/concentrate the produced Fe(TPTZ)2(2+) colored complex on the solid beads, resulting in a 625 times concentration of the target analyte without any other procedure. The detection limit of 0.1 μg dm(-3) was obtained, and the optimum conditions for the digestion procedure and color developing reaction was investigated and reported. According to the application of this method to real samples, the present SPS method is the best one because of the shorter analysis time, simpler operation and use of very low-cost equipment compared to the conventional methods, such as TPTZ solution spectrophotometric method after a 16 times concentration, ICP-MS and AAS.

Enhancement of Operating Efficiency Of The Central Coal-Preparation Plant of "MMK - UGOL" Ltd. Under Current Conditions

NASA Astrophysics Data System (ADS)

Basarygin, Maksim

2017-11-01

In this article the subject of enhancement of operating efficiency of the central coal-preparation plant of OOO "MMK-UGOL" is encompassed. Modern trends in the development of technologies and equipment for coal beneficiation are due to the following requirements: improving competitiveness of coal products, improvement of quality of marketable products, reduction of coal production cost, environmental requirements: polluting emission abatement, prepared coal saving, improvement of the effectiveness of resource conservation; complex mechanization and beneficiation process automation. In the article the contemporary problems of raw coal benefication under current conditions of the increased dilution of withdrawable coals with rock fractions are considered. Comparative analysis of efficiency of application of modern concentrating equipment under the conditions of the CCPP of OOO "MMK-UGOL" is carried out on the basis of research works. Particular attention is paid to dehydration of produced coal concentrate with content of volatile agents of more than 35.0% and content of fine-dispersed particles in flotation concentrate of more than 50.0%. Comparative analysis of the coal concentrate dehydration technologies is conducted.

Supercritical fluid extraction and separation of uranium from other actinides.

PubMed

Quach, Donna L; Mincher, Bruce J; Wai, Chien M

2014-06-15

The feasibility of separating U from nitric acid solutions of mixed actinides using tri-n-butylphosphate (TBP)-modified supercritical fluid carbon dioxide (sc-CO2) was investigated. The actinides U, Np, Pu, and Am were extracted into sc-CO2 modified with TBP from a range of nitric acid concentrations, in the absence of, or in the presence of, a number of traditional reducing and/or complexing agents to demonstrate the separation of these metals from U under sc-CO2 conditions. The separation of U from Pu using sc-CO2 was successful at nitric acid concentrations of less than 3M in the presence of acetohydroxamic acid (AHA) or oxalic acid (OA) to mitigate Pu extraction, and the separation of U from Np was successful at nitric acid concentrations of less than 1M in the presence of AHA, OA, or sodium nitrite to mitigate Np extraction. Americium was not well extracted under any condition studied. Copyright © 2014 Elsevier B.V. All rights reserved.

Supercritical Fluid Extraction and Separation of Uranium from Other Actinides

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

Donna L. Quach; Bruce J. Mincher; Chien M. Wai

2014-06-01

This paper investigates the feasibility of separating uranium from other actinides by using supercritical fluid carbon dioxide (sc-CO2) as a solvent modified with tri-n-butylphosphate (TBP) for the development of an extraction and counter current stripping technique, which would be a more efficient and environmentally benign technology for used nuclear fuel reprocessing compared to traditional solvent extraction. Several actinides (U(VI), Np(VI), Pu(IV), and Am(III)) were extracted in sc-CO2 modified with TBP over a range of nitric acid concentrations and then the actinides were exposed to reducing and complexing agents to suppress their extractability. According to this study, the separation of uraniummore » from plutonium in sc-CO2 modified with TBP was successful at nitric acid concentrations of less than 3 M in the presence of acetohydroxamic acid or oxalic acid, and the separation of uranium from neptunium was successful at nitric acid concentrations of less than 1 M in the presence of acetohydroxamic acid, oxalic acid, or sodium nitrite.« less

Evolutionary Agent-Based Simulation of the Introduction of New Technologies in Air Traffic Management

NASA Technical Reports Server (NTRS)

Yliniemi, Logan; Agogino, Adrian K.; Tumer, Kagan

2014-01-01

Accurate simulation of the effects of integrating new technologies into a complex system is critical to the modernization of our antiquated air traffic system, where there exist many layers of interacting procedures, controls, and automation all designed to cooperate with human operators. Additions of even simple new technologies may result in unexpected emergent behavior due to complex human/ machine interactions. One approach is to create high-fidelity human models coming from the field of human factors that can simulate a rich set of behaviors. However, such models are difficult to produce, especially to show unexpected emergent behavior coming from many human operators interacting simultaneously within a complex system. Instead of engineering complex human models, we directly model the emergent behavior by evolving goal directed agents, representing human users. Using evolution we can predict how the agent representing the human user reacts given his/her goals. In this paradigm, each autonomous agent in a system pursues individual goals, and the behavior of the system emerges from the interactions, foreseen or unforeseen, between the agents/actors. We show that this method reflects the integration of new technologies in a historical case, and apply the same methodology for a possible future technology.

Method and apparatus for enhanced detection of toxic agents

DOEpatents

Greenbaum, Elias [Knoxville, TN; Rodriguez, Jr., Miguel; Wu, Jie Jayne [Knoxville, TN; Qi, Hairong [Knoxville, TN

2012-06-12

A water quality analyzer for real-time detection according to the invention comprises a biased AC electro-osmosis (ACEO) cell for receiving a fluid to be analyzed having a plurality photosynthetic organisms therein, and concentrating the plurality photosynthetic organisms into at least one concentrated region. A photodetector is provided for obtaining a measured photosynthetic activity of the plurality of photosynthetic organisms in the concentrated region, wherein chemical, biological or radiological agents reduce a nominal photosynthetic activity of the photosynthetic organisms. An electronics package analyzes the measured photosynthetic activity to indicate a presence of the chemical, biological or radiological agents in the fluid.

Action of cholecystokinin and cholinergic agents on calcium transport in isolated pancreatic acinar cells.

PubMed Central

Gardner, J D; Conlon, T P; Kleveman, H L; Adams, T D; Ondetti, M A

1975-01-01

COOH-terminal octapeptide of cholecystokinin (CCK-octapeptide) and the cholinergic agent carbamylcholine each produced a fourfold stimulation of calcium outflux in guinea pig isolated pancreatic acinar cells. Neither agent altered calcium influx. Stimulation of calcium outflux was rapid and specific, was abolished by reducing the incubation temperature to 4 degrees C, and was a saturable function of the secretagogue concentration. The concentrations of CCK-octapeptide and carbamylcholine that produced half-maximal stimulation of calcium outflux were 3.1 x 10(-10) M and 4.9 x 10(-5) M, respectively. The cholinergic antagonist antropine competitively inhibited carbamylcholine stimulation of calcium outflux but did not alter stimulation produced by CCK-octapeptide. Stimulation of calcium outflux by maximal concentrations of carbamycholine plus CCK-octapeptide was the same as that produced by a maximal concentration of either agent alone.Calcium outflux became refractory to stimulation by secretagogues, and incubation with either CCK-ostapeptide or carbamylcholine produced a refractoriness to both agents. The relative potencies with CCK and its related fragments stimulated calcium outflux were CCK-octapeptide greater than heptapeptide greater than CCK greater than hexapeptide = gastrin. Secretin, glucagon, and vasoactive intestinal peptide, at concentrations as high as 10(-5) M, failed to alter calcium outflux and did not affect stimulation by CCK-octapeptide or by carbamycholine. Images PMID:1150877

Utility of an optically-based, micromechanical system for printing collagen fibers

PubMed Central

Paten, Jeffrey A.; Tilburey, Graham E.; Molloy, Eileen A.; Zareian, Ramin; Trainor, Christopher V.

2013-01-01

Collagen's success as the principal structural element in load-bearing, connective tissue has motivated the development of numerous engineering approaches designed to recapitulate native fibril morphology and strength. It has been shown recently that collagen fibers can be drawn from monomeric solution through a fiber forming buffer (FFB), followed by numerous additional treatments in a complex serial process. However, internal fibril alignment, packing and resultant mechanical behavior of the fibers have not been optimized and remain inferior to native tissue. Further, no system has been developed which permits simultaneous application of molecular crowding, measurement of applied load, and direct observation of polymerization dynamics during fiber printing. The ability to perform well-controlled investigations early in the process of fiber formation, which vary single input parameters (i.e. collagen concentration, crowding agent concentration, draw rate, flow rate, temperature, pH, etc.) should substantially improve fiber morphology and strength. We have thus designed, built, and tested a versatile, in situ, optically-based, micromechanical assay and fiber printing system which permits the correlation of parameter changes with mechanical properties of fibers immediately after deposition into an FFB. We demonstrate the sensitivity of the assay by detecting changes in the fiber mechanics in response to draw rate, collagen type, small changes in the molecular crowding agent concentration and to variations in pH. In addition we found the ability to observe fiber polymerization dynamics leads to intriguing new insights into collagen assembly behavior. PMID:23352045

Preparation and properties of inhalable nanocomposite particles for treatment of lung cancer.

PubMed

Tomoda, Keishiro; Ohkoshi, Takumi; Hirota, Keiji; Sonavane, Ganeshchandra S; Nakajima, Takehisa; Terada, Hiroshi; Komuro, Masahito; Kitazato, Kenji; Makino, Kimiko

2009-07-01

Nanoparticles have widely been studied in drug delivery research for targeting and controlled release. The aim of this article is application of nanoparticles as an inhalable agent for treatment of lung cancer. To deposit effectively deep the particles in the lungs, the PLGA nanoparticles loaded with the anticancer drug 6-{[2-(dimethylamino)ethyl]amino}-3-hydroxyl-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103) were prepared in the form of nanocomposite particles. The nanocomposite particles consist of the complex of drug-loaded nanoparticles and excipients. In this study, the anticancer effects of the nanocomposite particles against the lung cancer cell line A549. Also, the concentration of TAS-103 in blood and lungs were determined after administration of the nanocomposite particles by inhalation to rats. TAS-103-loaded PLGA nanoparticles were prepared with 5% and 10% of loading ratio by spray drying method with trehalose as an excipient. The 5% drug-loaded nanocomposite particles were more suitable for inhalable agent because of the sustained release of TAS-103 and higher FPF value. Cytotoxicity of nanocomposite particles against A549 cells was higher than that of free drug. When the nanocomposite particles were administered in rats by inhalation, drug concentration in lung was much higher than that in plasma. Furthermore, drug concentration in lungs administered by inhalation of nanocomposite particles was much higher than that after intravenous administration of free drug. From these results, the nanocomposite particle systems could be promising for treatment of lung cancer.

Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model.

PubMed

Grottke, Oliver; van Ryn, Joanne; Spronk, Henri M H; Rossaint, Rolf

2014-02-05

New oral anticoagulants are effective alternatives to warfarin. However, no specific reversal agents are available for life-threatening bleeding or emergency surgery. Using a porcine model of trauma, this study assessed the ability of prothrombin complex concentrate (PCC), activated PCC (aPCC), recombinant FVIIa (rFVIIa) and a specific antidote to dabigatran (aDabi-Fab) to reverse the anticoagulant effects of dabigatran. Dabigatran etexilate (DE) was given orally for 3 days (30 mg/kg bid) and intravenously on day 4 to achieve consistent, supratherapeutic concentrations of dabigatran. Blood samples were collected at baseline, after oral DE, after intravenous dabigatran, and 60 minutes post-injury. PCC (30 and 60 U/kg), aPCC (30 and 60 U/kg), rFVIIa (90 and 180 μg/kg) and antidote (60 and 120 mg/kg) were added to blood samples ex-vivo. Coagulation was assessed by thromboelastometry, global coagulation assays and diluted thrombin time. Plasma concentrations of dabigatran were 380 ± 106 ng/ml and 1423 ± 432 ng/ml after oral and intravenous administration, respectively, and all coagulation parameters were affected by dabigatran. Both PCCs and aDabi-Fab, but not rFVIIa, reversed the effects of dabigatran on thromboelastometry parameters and prothrombin time. In contrast, aPTT was only normalised by aDabi-Fab. Plasma concentration (activity) of dabigatran remained elevated after PCC and rFVIIa therapy, but was not measureable after aDabi-Fab. In conclusion, PCC and aPCC were effective in reducing the anticoagulant effects of dabigatran under different conditions, while aDabi-Fab fully corrected all coagulation measures and decreased the plasma concentration of dabigatran below the limit of detection. No significant effects were observed with rFVIIa.

Miniaturized and direct spectrophotometric multi-sample analysis of trace metals in natural waters.

PubMed

Albendín, Gemma; López-López, José A; Pinto, Juan J

2016-03-15

Trends in the analysis of trace metals in natural waters are mainly based on the development of sample treatment methods to isolate and pre-concentrate the metal from the matrix in a simpler extract for further instrumental analysis. However, direct analysis is often possible using more accessible techniques such as spectrophotometry. In this case a proper ligand is required to form a complex that absorbs radiation in the ultraviolet-visible (UV-Vis) spectrum. In this sense, the hydrazone derivative, di-2-pyridylketone benzoylhydrazone (dPKBH), forms complexes with copper (Cu) and vanadium (V) that absorb light at 370 and 395 nm, respectively. Although spectrophotometric methods are considered as time- and reagent-consuming, this work focused on its miniaturization by reducing the volume of sample as well as time and cost of analysis. In both methods, a micro-amount of sample is placed into a microplate reader with a capacity for 96 samples, which can be analyzed in times ranging from 5 to 10 min. The proposed methods have been optimized using a Box-Behnken design of experiments. For Cu determination, concentration of phosphate buffer solution at pH 8.33, masking agents (ammonium fluoride and sodium citrate), and dPKBH were optimized. For V analysis, sample (pH 4.5) was obtained using acetic acid/sodium acetate buffer, and masking agents were ammonium fluoride and 1,2-cyclohexanediaminetetraacetic acid. Under optimal conditions, both methods were applied to the analysis of certified reference materials TMDA-62 (lake water), LGC-6016 (estuarine water), and LGC-6019 (river water). In all cases, results proved the accuracy of the method. Copyright © 2015 Elsevier Inc. All rights reserved.

The human milk protein-lipid complex HAMLET sensitizes bacterial pathogens to traditional antimicrobial agents.

PubMed

Marks, Laura R; Clementi, Emily A; Hakansson, Anders P

2012-01-01

The fight against antibiotic resistance is one of the most significant challenges to public health of our time. The inevitable development of resistance following the introduction of novel antibiotics has led to an urgent need for the development of new antibacterial drugs with new mechanisms of action that are not susceptible to existing resistance mechanisms. One such compound is HAMLET, a natural complex from human milk that kills Streptococcus pneumoniae (the pneumococcus) using a mechanism different from common antibiotics and is immune to resistance-development. In this study we show that sublethal concentrations of HAMLET potentiate the effect of common antibiotics (penicillins, macrolides, and aminoglycosides) against pneumococci. Using MIC assays and short-time killing assays we dramatically reduced the concentrations of antibiotics needed to kill pneumococci, especially for antibiotic-resistant strains that in the presence of HAMLET fell into the clinically sensitive range. Using a biofilm model in vitro and nasopharyngeal colonization in vivo, a combination of HAMLET and antibiotics completely eradicated both biofilms and colonization in mice of both antibiotic-sensitive and resistant strains, something each agent alone was unable to do. HAMLET-potentiation of antibiotics was partially due to increased accessibility of antibiotics to the bacteria, but relied more on calcium import and kinase activation, the same activation pathway HAMLET uses when killing pneumococci by itself. Finally, the sensitizing effect was not confined to species sensitive to HAMLET. The HAMLET-resistant respiratory species Acinetobacter baumanii and Moraxella catarrhalis were all sensitized to various classes of antibiotics in the presence of HAMLET, activating the same mechanism as in pneumococci. Combined these results suggest the presence of a conserved HAMLET-activated pathway that circumvents antibiotic resistance in bacteria. The ability to activate this pathway may extend the lifetime of the current treatment arsenal.

Preservation of samples for dissolved mercury

USGS Publications Warehouse

Hamlin, S.N.

1989-01-01

Water samples for dissolved mercury requires special treatment because of the high chemical mobility and volatility of this element. Widespread use of mercury and its compounds has provided many avenues for contamination of water. Two laboratory tests were done to determine the relative permeabilities of glass and plastic sample bottles to mercury vapor. Plastic containers were confirmed to be quite permeable to airborne mercury, glass containers were virtually impermeable. Methods of preservation include the use of various combinations of acids, oxidants, and complexing agents. The combination of nitric acid and potassium dichromate successfully preserved mercury in a large variety of concentrations and dissolved forms. Because this acid-oxidant preservative acts as a sink for airborne mercury and plastic containers are permeable to mercury vapor, glass bottles are preferred for sample collection. To maintain a healthy work environment and minimize the potential for contamination of water samples, mercury and its compounds are isolated from the atmosphere while in storage. Concurrently, a program to monitor environmental levels of mercury vapor in areas of potential contamination is needed to define the extent of mercury contamination and to assess the effectiveness of mercury clean-up procedures.Water samples for dissolved mercury require special treatment because of the high chemical mobility and volatility of this element. Widespread use of mercury and its compounds has provided many avenues for contamination of water. Two laboratory tests were done to determine the relative permeabilities of glass and plastic sample bottles to mercury vapor. Plastic containers were confirmed to be quite permeable to airborne mercury, glass containers were virtually impermeable. Methods of preservation include the use of various combinations of acids, oxidants, and complexing agents. The combination of nitric acid and potassium dichromate successfully preserved mercury in a large variety of concentrations and dissolved forms.

The Human Milk Protein-Lipid Complex HAMLET Sensitizes Bacterial Pathogens to Traditional Antimicrobial Agents

PubMed Central

Marks, Laura R.; Clementi, Emily A.; Hakansson, Anders P.

2012-01-01

The fight against antibiotic resistance is one of the most significant challenges to public health of our time. The inevitable development of resistance following the introduction of novel antibiotics has led to an urgent need for the development of new antibacterial drugs with new mechanisms of action that are not susceptible to existing resistance mechanisms. One such compound is HAMLET, a natural complex from human milk that kills Streptococcus pneumoniae (the pneumococcus) using a mechanism different from common antibiotics and is immune to resistance-development. In this study we show that sublethal concentrations of HAMLET potentiate the effect of common antibiotics (penicillins, macrolides, and aminoglycosides) against pneumococci. Using MIC assays and short-time killing assays we dramatically reduced the concentrations of antibiotics needed to kill pneumococci, especially for antibiotic-resistant strains that in the presence of HAMLET fell into the clinically sensitive range. Using a biofilm model in vitro and nasopharyngeal colonization in vivo, a combination of HAMLET and antibiotics completely eradicated both biofilms and colonization in mice of both antibiotic-sensitive and resistant strains, something each agent alone was unable to do. HAMLET-potentiation of antibiotics was partially due to increased accessibility of antibiotics to the bacteria, but relied more on calcium import and kinase activation, the same activation pathway HAMLET uses when killing pneumococci by itself. Finally, the sensitizing effect was not confined to species sensitive to HAMLET. The HAMLET-resistant respiratory species Acinetobacter baumanii and Moraxella catarrhalis were all sensitized to various classes of antibiotics in the presence of HAMLET, activating the same mechanism as in pneumococci. Combined these results suggest the presence of a conserved HAMLET-activated pathway that circumvents antibiotic resistance in bacteria. The ability to activate this pathway may extend the lifetime of the current treatment arsenal. PMID:22905269

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

Chen, Yen-Wei; Drury, Jeanie L.; Moussi, Joelle

Monosodium titanates (MST) are a relatively novel form of particulate titanium dioxide that have been proposed for biological use as metal sorbents or delivery agents, most recently calcium (II). In these roles, the toxicity of the titanate or its metal complex is crucial to its biological utility. The aim of this study was to determine the cytotoxicity of MST and MST-calcium complexes with MC3T3 osteoblast-like cells; MST-Ca(II) complexes could be useful to promote bone formation in various hard tissue applications. MC3T3 cells were exposed to native MST or MST-Ca(II) complexes for 24–72 h. A CellTiter-Blue ® assay was employed tomore » assess the metabolic activity of the cells. The results showed that MST and MST-Ca(II) suppressed MC3T3 metabolic activity significantly in a dose-, time-, and cell-density-dependent fashion. MST-Ca(II) suppressed MC3T3 metabolism in a statistically identical manner as native MST at all concentrations. We concluded that MST and MST-Ca(II) are significantly cytotoxic to MC3T3 cells through a mechanism yet unknown; this is a potential problem to the biological utility of these complexes.« less

Prospects of molybdenum and rhenium octahedral cluster complexes as X-ray contrast agents.

PubMed

Krasilnikova, Anna A; Shestopalov, Michael A; Brylev, Konstantin A; Kirilova, Irina A; Khripko, Olga P; Zubareva, Kristina E; Khripko, Yuri I; Podorognaya, Valentina T; Shestopalova, Lidiya V; Fedorov, Vladimir E; Mironov, Yuri V

2015-03-01

Investigation of new X-ray contrast media for radiography is an important field of science since discovering of X-rays in 1895. Despite the wide diversity of available X-ray contrast media the toxicity, especially nephrotoxicity, is still a big problem to be solved. The octahedral metal-cluster complexes of the general formula [{M6Q8}L6] can be considered as quite promising candidates for the role of new radiocontrast media due to the high local concentration of heavy elements, high tuning ability of ligand environment and low toxicity. To exemplify this, the X-ray computed tomography experiments for the first time were carried out on some octahedral cluster complexes of molybdenum and rhenium. Based on the obtained data it was proposed to investigate the toxicological proprieties of cluster complex Na2H8[{Re6Se8}(P(CH2CH2CONH2)(CH2CH2COO)2)6]. Observed low cytotoxic and acute toxic effects along with rapid renal excretion of the cluster complex evidence its perspective as an X-ray contrast media for radiography. Copyright © 2014 Elsevier Inc. All rights reserved.

Optimization of chlorphenesin emulgel formulation.

PubMed

Mohamed, Magdy I

2004-10-11

This study was conducted to develop an emulgel formulation of chlorphenesin (CHL) using 2 types of gelling agents: hydroxypropylmethyl cellulose (HPMC) and Carbopol 934. The influence of the type of the gelling agent and the concentration of both the oil phase and emulsifying agent on the drug release from the prepared emulgels was investigated using a 2(3) factorial design. The prepared emulgels were evaluated for their physical appearance, rheological behavior, drug release, antifungal activity, and stability. Commercially available CHL topical powder was used for comparison. All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, spreadability, and pH value. They also exhibited higher drug release and antifungal activity than the CHL powder. It was found that the emulsifying agent concentration had the most pronounced effect on the drug release from the emulgels followed by the oil phase concentration and finally the type of the gelling agent. The drug release from all the emulgels was found to follow diffusion-controlled mechanism. Rheological studies revealed that the CHL emulgels exhibited a shear-thinning behavior with thixotropy. Stability studies showed that the physical appearance, rheological properties, drug release, and antifungal activity in all the prepared emulgels remained unchanged upon storage for 3 months. As a general conclusion, it was suggested that the CHL emulgel formulation prepared with HPMC with the oil phase concentration in its low level and emulsifying agent concentration in its high level was the formula of choice since it showed the highest drug release and antifungal activity.

Sensitivity of human dental pulp cells to eighteen chemical agents used for endodontic treatments in dentistry.

PubMed

Kobayashi, Morio; Tsutsui, Takeo W; Kobayashi, Tomoko; Ohno, Maki; Higo, Yukari; Inaba, Tomohiro; Tsutsui, Takeki

2013-01-01

To determine the adverse effects against human dental pulp tissue, the sensitivity of human dental pulp cells (D824 cells) to 18 chemical agents used for endodontic treatments in dentistry was examined. The cytotoxicity, as determined by a decrease in colony-forming ability of cells treated with the chemical agents, increased as the concentration increased. As a quantitative measure of the cytotoxic effect, LC(50), the concentration which induces a 50% lethality, was extrapolated from the concentration-response curves. The rank of the chemical agents according to their cytotoxic effect (LC(50)) was sodium arsenite > formaldehyde > hydrogen peroxide > zinc oxide > thymol ≈ iodoform ≈ eugenol > guaiacol > ethylenediaminetetraacetic acid ≈ iodine > procaine > lidocaine ≈ chloramphenicol ≈ m-cresol > calcium hydroxide ≈ sodium hypochlorite ≈ phenol ≈ p-phenolsulfonic acid. To compare the cytotoxicity and the levels of apoptosis and mRNA expression of five genes related to the function of dental pulp tissue, D824 cells treated with the LC(50) concentrations of chemical agents were assayed by the TUNEL method and quantitative reverse transcription polymerase chain reaction analysis, respectively. The inducibility of apoptotic cells and the level of mRNA expression of the genes varied with the chemical agents, indicating that both effects occurred independent of the rank of cytotoxic effect of the chemical agents. The results not only provide information concerning cytotoxicity of various chemical agents to human dental pulp cells, but also show an insight into the diversity of the pharmacodynamic action of the chemical agents.

Smart Swarms of Bacteria-Inspired Agents with Performance Adaptable Interactions

PubMed Central

Shklarsh, Adi; Ariel, Gil; Schneidman, Elad; Ben-Jacob, Eshel

2011-01-01

Collective navigation and swarming have been studied in animal groups, such as fish schools, bird flocks, bacteria, and slime molds. Computer modeling has shown that collective behavior of simple agents can result from simple interactions between the agents, which include short range repulsion, intermediate range alignment, and long range attraction. Here we study collective navigation of bacteria-inspired smart agents in complex terrains, with adaptive interactions that depend on performance. More specifically, each agent adjusts its interactions with the other agents according to its local environment – by decreasing the peers' influence while navigating in a beneficial direction, and increasing it otherwise. We show that inclusion of such performance dependent adaptable interactions significantly improves the collective swarming performance, leading to highly efficient navigation, especially in complex terrains. Notably, to afford such adaptable interactions, each modeled agent requires only simple computational capabilities with short-term memory, which can easily be implemented in simple swarming robots. PMID:21980274

Smart swarms of bacteria-inspired agents with performance adaptable interactions.

PubMed

Shklarsh, Adi; Ariel, Gil; Schneidman, Elad; Ben-Jacob, Eshel

2011-09-01

Collective navigation and swarming have been studied in animal groups, such as fish schools, bird flocks, bacteria, and slime molds. Computer modeling has shown that collective behavior of simple agents can result from simple interactions between the agents, which include short range repulsion, intermediate range alignment, and long range attraction. Here we study collective navigation of bacteria-inspired smart agents in complex terrains, with adaptive interactions that depend on performance. More specifically, each agent adjusts its interactions with the other agents according to its local environment--by decreasing the peers' influence while navigating in a beneficial direction, and increasing it otherwise. We show that inclusion of such performance dependent adaptable interactions significantly improves the collective swarming performance, leading to highly efficient navigation, especially in complex terrains. Notably, to afford such adaptable interactions, each modeled agent requires only simple computational capabilities with short-term memory, which can easily be implemented in simple swarming robots.

Non-specific vaginitis or vaginitis of undetermined aetiology.

PubMed

Faro, S; Phillips, L E

1987-01-01

Vaginitis is a complex syndrome that is probably the most common outpatient disease seen by the gynaecologist. The specific aetiologies of vaginitis are many. One of the most common entities, however, is "non-specific vaginitis" which can be subdivided into: Gardnerella vaginitis, anaerobic vaginosis, and vaginitis of undetermined aetiology. The role of Gardnerella as a causative agent for vaginitis has been studied in depth but its specific role remains controversial. Anaerobic vaginosis can be diagnosed by noting on microscopic examination the presence of clue cells, free-floating bacteria and numerous white blood cells (WBC's). Culturing an aliquot of the vaginal discharge reveals a high number of anaerobes. In addition, this condition responds to antibiotics effective against anaerobes, e.g., metronidazole. Vaginitis of undetermined aetiology is more complex and is characterized by a purulent vaginal discharge, a pH of 4.0-4.6, numerous WBC's, and a high concentration of bacteria. The microbiology of this vaginitis includes many facultative Gram-negative rods and Gram-positive cocci. Anaerobes may be present but do not make up a large component of the endogenous microflora. This condition does not respond to the usual antibiotic therapies employed in treating bacterial vaginitis. Since this condition appears to be primarily an inflammatory reaction, it may be responsive to topical antiinflammatory agents such as benzydamine.

The Reversal of Direct Oral Anticoagulants in Animal Models

PubMed Central

Honickel, Markus; Akman, Necib; Grottke, Oliver

2017-01-01

ABSTRACT Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. The optimal strategy for DOAC reversal is being refined, and may include use of hemostatic agents such as prothrombin complex concentrates (PCCs; a source of concentrated clotting factors), or DOAC-specific antidotes (which bind their target DOAC to abrogate its activity). Though promising, most specific antidotes are still in development. Preclinical animal research is the key to establishing the efficacy and safety of potential reversal agents. Here, we summarize published preclinical animal studies on reversal of DOAC anticoagulation. These studies (n = 26) were identified via a PubMed search, and used rodent, rabbit, pig, and non-human primate models. The larger of these animals have the advantages of similar blood volume/hemodynamics to humans, and can be used to model polytrauma. We find that in addition to varied species being used, there is variability in the models and assays used between studies; we suggest that blood loss (bleeding volume) is the most clinically relevant measure of DOAC anticoagulation-related bleeding and its reversal. The studies covered indicate that both PCCs and specific reversal agents have the potential to be used as part of a clinical strategy for DOAC reversal. For the future, we advocate the development and use of standardized, clinically, and pharmacologically relevant animal models to study novel DOAC reversal strategies. PMID:28471371

Remediation of Pb/Cr co-contaminated soil using electrokinetic process and approaching electrode technique.

PubMed

Ng, Yee-Sern; Sen Gupta, Bhaskar; Hashim, Mohd Ali

2016-01-01

Electrokinetic process has emerged as an important tool for remediating heavy metal-contaminated soil. The process can concentrate heavy metals into smaller soil volume even in the absence of hydraulic flow. This makes it an attractive soil pre-treatment method before other remediation techniques are applied such that the chemical consumption in the latter stage can be reduced. The present study evaluates the feasibility of electrokinetic process in concentrating lead (Pb) and chromium (Cr) in a co-contaminated soil using different types of wetting agents, namely 0.01 M NaNO3, 0.1 M citric acid and 0.1 M EDTA. The data obtained showed that NaNO3 and citric acid resulted in poor Pb electromigration in this study. As for Cr migration, these agents were also found to give lower electromigration rate especially at low pH region as a result of Cr(VI) adsorption and possible reduction into Cr(III). In contrast, EDTA emerged as the best wetting agent in this study as it formed water-soluble anionic complexes with both Pb and Cr. This provided effective one-way electromigration towards the anode for both ions, and they were accumulated into smaller soil volume with an enrichment ratio of 1.55-1.82. A further study on the application of approaching cathode in EDTA test showed that soil alkalisation was achieved, but this did not provide significant enhancement on electromigration for Pb and Cr. Nevertheless, the power consumption for electrokinetic process was decreased by 22.5%.

Multichannel imaging to quantify four classes of pharmacokinetic distribution in tumors

PubMed Central

Bhatnagar, Sumit; Deschenes, Emily; Liao, Jianshan; Cilliers, Cornelius; Thurber, Greg M.

2014-01-01

Low and heterogeneous delivery of drugs and imaging agents to tumors results in decreased efficacy and poor imaging results. Systemic delivery involves a complex interplay of drug properties and physiological factors, and heterogeneity in the tumor microenvironment makes predicting and overcoming these limitations exceptionally difficult. Theoretical models have indicated that there are four different classes of pharmacokinetic behavior in tissue, depending on the fundamental steps in distribution. In order to study these limiting behaviors, we used multichannel fluorescence microscopy and stitching of high-resolution images to examine the distribution of four agents in the same tumor microenvironment. A validated generic partial differential equation model with a graphical user interface was used to select fluorescent agents exhibiting these four classes of behavior, and the imaging results agreed with predictions. BODIPY-FL exhibited higher concentrations in tissue with high blood flow, cetuximab gave perivascular distribution limited by permeability, high plasma protein and target binding resulted in diffusion-limited distribution for Hoechst 33342, and Integrisense 680 was limited by the number of binding sites in the tissue. Together, the probes and simulations can be used to investigate distribution in other tumor models, predict tumor drug distribution profiles, and design and interpret in vivo experiments. PMID:25048378

Tracing and quantification of pharmaceuticals using MR imaging and spectroscopy at clinical MRI system

NASA Astrophysics Data System (ADS)

Jeong, Eun-Kee; Liu, Xin; Shi, Xianfeng; Yu, Y. Bruce; Lu, Zeng-Rong

2012-10-01

Magnetic resonance imaging (MRI) and spectroscopy (MRS) is very powerful modality for imaging and localized investigation of biological tissue. Medical MRI measures nuclear magnetization of the water protons, which consists of 70 % of our body. MRI provides superior contrast among different soft tissues to all other existing medical imaging modalities, including ultrasound, X-ray CT, PET, and SPECT. In principle, MRI/S may be an ideal non-invasive tool for drug delivery research. However, because of its low sensitivity, a large dose is required for tracing pharmaceuticals. Therefore, its use for imaging of pharmaceuticals is very limited mostly to molecules that contain a paramagnetic metal ion, such as gadolinium (Gd3+) and manganese (Mn2+). The paramagnetic metal ion provides a large fluctuating magnetic field at the proton in the water molecule via a coordinate site. The measurement of local drug concentration is the first step for further quantification. Local concentration of the paramagnetic-ion based MRI contrast agent can be indirectly measured via the change in the water signal intensity. 19F MRI/S of fluorinated complex may be an option for drug delivery and tracing agent, because the fluorinated molecule may be directly detected due to its large magnetic moment (94 % of proton) and 100 % abundance.

Using an agent-based model to analyze the dynamic communication network of the immune response

PubMed Central

2011-01-01

Background The immune system behaves like a complex, dynamic network with interacting elements including leukocytes, cytokines, and chemokines. While the immune system is broadly distributed, leukocytes must communicate effectively to respond to a pathological challenge. The Basic Immune Simulator 2010 contains agents representing leukocytes and tissue cells, signals representing cytokines, chemokines, and pathogens, and virtual spaces representing organ tissue, lymphoid tissue, and blood. Agents interact dynamically in the compartments in response to infection of the virtual tissue. Agent behavior is imposed by logical rules derived from the scientific literature. The model captured the agent-to-agent contact history, and from this the network topology and the interactions resulting in successful versus failed viral clearance were identified. This model served to integrate existing knowledge and allowed us to examine the immune response from a novel perspective directed at exploiting complex dynamics, ultimately for the design of therapeutic interventions. Results Analyzing the evolution of agent-agent interactions at incremental time points from identical initial conditions revealed novel features of immune communication associated with successful and failed outcomes. There were fewer contacts between agents for simulations ending in viral elimination (win) versus persistent infection (loss), due to the removal of infected agents. However, early cellular interactions preceded successful clearance of infection. Specifically, more Dendritic Agent interactions with TCell and BCell Agents, and more BCell Agent interactions with TCell Agents early in the simulation were associated with the immune win outcome. The Dendritic Agents greatly influenced the outcome, confirming them as hub agents of the immune network. In addition, unexpectedly high frequencies of Dendritic Agent-self interactions occurred in the lymphoid compartment late in the loss outcomes. Conclusions An agent-based model capturing several key aspects of complex system dynamics was used to study the emergent properties of the immune response to viral infection. Specific patterns of interactions between leukocyte agents occurring early in the response significantly improved outcome. More interactions at later stages correlated with persistent inflammation and infection. These simulation experiments highlight the importance of commonly overlooked aspects of the immune response and provide insight into these processes at a resolution level exceeding the capabilities of current laboratory technologies. PMID:21247471

Gd-DTPA T1 relaxivity in brain tissue obtained by convection-enhanced delivery, magnetic resonance imaging and emission spectroscopy

NASA Astrophysics Data System (ADS)

Haar, Peter J.; Broaddus, William C.; Chen, Zhi-jian; Fatouros, Panos P.; Gillies, George T.; Corwin, Frank D.

2010-06-01

A common approach to quantify gadolinium (Gd) contrast agents involves measuring the post-contrast change in T1 rate and then using the constant T1 relaxivity R to determine the contrast agent concentration. Because this method is fast and non-invasive, it could be potentially valuable in many areas of brain research. However, to accurately measure contrast agent concentrations in the brain, the T1 relaxivity R of the specific agent must be accurately known. Furthermore, the macromolecular content and compartmentalization of the brain extracellular space (ECS) are expected to significantly alter R from values measured in aqueous solutions. In this study, the T1 relaxivity R of gadolinium-diethylene-triamine penta-acetic acid (Gd-DTPA) was measured following direct interstitial infusions of three different contrast agent concentrations to the parenchyma of rat brains. Changes in magnetic resonance (MR) T1 values were compared to brain slice concentrations determined with inductively coupled plasma atomic emission spectroscopy (ICP-AES) to determine R in 15 rats. Additionally, samples of cerebrospinal fluid, blood and urine were analyzed to evaluate possible Gd-DTPA clearance from the brain. The T1 relaxivity R of Gd-DTPA in the brain ECS was measured to be 5.35 (mM s)-1 in a 2.4 T field. This value is considerably higher than estimations used in studies by other groups. Measurements of brain Gd-DTPA tissue concentrations using MRI and ICP-AES demonstrated a high degree of coincidence. Clearance of Gd-DTPA was minimal at the time point immediately after infusion. These results suggest that the environment of the brain does in fact significantly affect Gd T1 relaxivity, and that MRI can accurately measure contrast agent concentrations when this relaxivity is well characterized.

Echinacea complex--chemical view and anti-asthmatic profile.

PubMed

Šutovská, Martina; Capek, Peter; Kazimierová, Ivana; Pappová, Lenka; Jošková, Marta; Matulová, Mária; Fraňová, Soňa; Pawlaczyk, Izabela; Gancarz, Roman

2015-12-04

Echinacea purpurea (L.) Moench is one of the mostly used herbs in the traditional medicine for the treatment of respiratory diseases. Modern interest in Echinacea is directed to its immunomodulatory activity. Recent studies have shown that secretion of asthma-related cytokines in the bronchial epithelial cells can be reversed by Echinacea preparations. To examine the pharmacodynamics profile of Echinacea active principles, a complex has been isolated from its flowers by alkaline extraction and has been tested using an animal model of allergic asthma. The structural features of Echinacea purpurea complex was determined using chemical and spectroscopic methods. Allergic inflammation of the airways was induced by repetitive exposure of guinea pigs to ovalbumin. Echinacea complex was then administered 14 days in 50mg/kg b.w. daily dose perorally. Bronchodilatory effect was verified as decrease in the specific airway resistance (sRaw) in vivo and by reduced contraction amplitude (mN) of tracheal and pulmonary smooth muscle to cumulative concentrations of acetylcholine and histamine in vitro. The impact on mucociliary clearance evaluated measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software. Anti-inflammatory effect of Echinacea complex was verified by changes in exhaled NO levels and by Bio-Plex® assay of Th2 cytokine concentrations (IL-4, IL-5, IL-13 and TNF-alpha) in serum and bronchoalveolar lavage fluid (BALF). Chemical and spectroscopic studies confirmed the presence of carbohydrates, phenolic compounds and proteins, as well as the dominance of rhamnogalacturonan and arabinogalactan moieties in Echinacea complex. The significant decrease in sRaw values and suppressed histamine and acetylcholine-induced contractile amplitude of isolated airways smooth muscle that were similar to effects of control drug salbutamol confirmed Echinacea complex bronchodilatory activity. The anti-inflammatory effect was comparable with that of control agent budesonide and was verified as significantly reduced exhaled NO levels and concentration of Th2 cytokines in serum and BALF. The values of CBF were changed only insignificantly on long-term administration of Echinacea complex suggested its minimal negative impact on mucociliary clearance. Pharmacodynamic studies have confirmed significant bronchodilatory and anti-inflammatory effects of Echinacea complex that was similar to effects of classic synthetic drugs. Thus, results provide a scientific basis for the application of this herb in traditional medicine as a supplementary treatment of allergic disorders of the airways, such as asthma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

SPARK: A Framework for Multi-Scale Agent-Based Biomedical Modeling.

PubMed

Solovyev, Alexey; Mikheev, Maxim; Zhou, Leming; Dutta-Moscato, Joyeeta; Ziraldo, Cordelia; An, Gary; Vodovotz, Yoram; Mi, Qi

2010-01-01

Multi-scale modeling of complex biological systems remains a central challenge in the systems biology community. A method of dynamic knowledge representation known as agent-based modeling enables the study of higher level behavior emerging from discrete events performed by individual components. With the advancement of computer technology, agent-based modeling has emerged as an innovative technique to model the complexities of systems biology. In this work, the authors describe SPARK (Simple Platform for Agent-based Representation of Knowledge), a framework for agent-based modeling specifically designed for systems-level biomedical model development. SPARK is a stand-alone application written in Java. It provides a user-friendly interface, and a simple programming language for developing Agent-Based Models (ABMs). SPARK has the following features specialized for modeling biomedical systems: 1) continuous space that can simulate real physical space; 2) flexible agent size and shape that can represent the relative proportions of various cell types; 3) multiple spaces that can concurrently simulate and visualize multiple scales in biomedical models; 4) a convenient graphical user interface. Existing ABMs of diabetic foot ulcers and acute inflammation were implemented in SPARK. Models of identical complexity were run in both NetLogo and SPARK; the SPARK-based models ran two to three times faster.

MRI contrast agent concentration and tumor interstitial fluid pressure.

PubMed

Liu, L J; Schlesinger, M

2016-10-07

The present work describes the relationship between tumor interstitial fluid pressure (TIFP) and the concentration of contrast agent for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We predict the spatial distribution of TIFP based on that of contrast agent concentration. We also discuss the cases for estimating tumor interstitial volume fraction (void fraction or porosity of porous medium), ve, and contrast volume transfer constant, K(trans), by measuring the ratio of contrast agent concentration in tissue to that in plasma. A linear fluid velocity distribution may reflect a quadratic function of TIFP distribution and lead to a practical method for TIFP estimation. To calculate TIFP, the parameters or variables should preferably be measured along the direction of the linear fluid velocity (this is in the same direction as the gray value distribution of the image, which is also linear). This method may simplify the calculation for estimating TIFP. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

CHLORPYRIFOS DEVELOPMENTAL NEUROTOXICITY: INTERACTION WITH GLUCOCORTICOIDS IN PC12 CELLS

PubMed Central

Slotkin, Theodore A.; Card, Jennifer; Seidler, Frederic J.

2012-01-01

Prenatal coexposures to glucocorticoids and organophosphate pesticides are widespread. Glucocorticoids are elevated by maternal stress and are commonly given in preterm labor; organophosphate exposures are virtually ubiquitous. We used PC12 cells undergoing neurodifferentiation in order to assess whether dexamethasone enhances the developmental neurotoxicity of chlorpyrifos, focusing on concentrations relevant to human exposures. By themselves, each agent reduced the number of cells and the combined exposure elicited a correspondingly greater effect than with either agent alone. There was no general cytotoxicity, as cell growth was actually enhanced, and again, the combined treatment evoked greater cellular hypertrophy than with the individual compounds. The effects on neurodifferentiation were more complex. Chlorpyrifos alone had a promotional effect on neuri to genesis whereas dexamethasone impaired it; combined treatment showed an overall impairment greater than that seen with dexamethasone alone. The effect of chlorpyrifos on differentiation into specific neurotransmitter phenotypes was shifted by dexamethasone. Either agent alone promoted differentiation into the dopaminergic phenotype at the expense of the cholinergic phenotype. However, in dexamethasone-primed cells, chlorpyrifos actually enhanced cholinergic neurodifferentiation instead of suppressing this phenotype. Our results indicate that developmental exposure to glucocorticoids, either in the context of stress or the therapy of preterm labor, could enhance the developmental neurotoxicity of organophosphates and potentially of other neurotoxicants, as well as producing neurobehavioral outcomes distinct from those seen with either individual agent. PMID:22796634

DNA condensing effects and sequence selectivity of DNA binding of antitumor noncovalent polynuclear platinum complexes.

PubMed

Malina, Jaroslav; Farrell, Nicholas P; Brabec, Viktor

2014-02-03

The noncovalent analogues of antitumor polynuclear platinum complexes represent a structurally discrete class of platinum drugs. Their chemical and biological properties differ significantly from those of most platinum chemotherapeutics, which bind to DNA in a covalent manner by formation of Pt-DNA adducts. In spite of the fact that these noncovalent polynuclear platinum complexes contain no leaving groups, they have been shown to bind to DNA with high affinity. We report here on the DNA condensation properties of a series of noncovalent analogues of antitumor polynuclear platinum complexes described by biophysical and biochemical methods. The results demonstrate that these polynuclear platinum compounds are capable of inducing DNA condensation at more than 1 order of magnitude lower concentrations than conventional spermine. Atomic force microscopy studies of DNA condensation confined to a mica substrate have revealed that the DNA morphologies become more compact with increasing concentration of the platinum complexes. Moreover, we also found that the noncovalent polynuclear platinum complex [{Pt(NH3)3}2-μ-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}](6+) (TriplatinNC-A) binds to DNA in a sequence-dependent manner, namely, to A/T-rich sequences and A-tract regions, and that noncovalent polynuclear platinum complexes protect DNA from enzymatic cleavage by DNase I. The results suggest that mechanisms of antitumor and cytotoxic activities of these complexes may be associated with their unique ability to condense DNA along with their sequence-specific DNA binding. Owing to their high cellular accumulation, it is also reasonable to suggest that their mechanism of action is based on the competition with naturally occurring DNA condensing agents, such as polyamines spermine, spermidine, and putrescine, for intracellular binding sites, resulting in the disturbance of the correct binding of regulatory proteins initiating the onset of apoptosis.

Cytotoxicity of Titanate-Calcium Complexes to MC3T3 Osteoblast-Like Cells

DOE PAGES

Chen, Yen-Wei; Drury, Jeanie L.; Moussi, Joelle; ...

2016-11-30

Monosodium titanates (MST) are a relatively novel form of particulate titanium dioxide that have been proposed for biological use as metal sorbents or delivery agents, most recently calcium (II). In these roles, the toxicity of the titanate or its metal complex is crucial to its biological utility. The aim of this study was to determine the cytotoxicity of MST and MST-calcium complexes with MC3T3 osteoblast-like cells; MST-Ca(II) complexes could be useful to promote bone formation in various hard tissue applications. MC3T3 cells were exposed to native MST or MST-Ca(II) complexes for 24–72 h. A CellTiter-Blue ® assay was employed tomore » assess the metabolic activity of the cells. The results showed that MST and MST-Ca(II) suppressed MC3T3 metabolic activity significantly in a dose-, time-, and cell-density-dependent fashion. MST-Ca(II) suppressed MC3T3 metabolism in a statistically identical manner as native MST at all concentrations. We concluded that MST and MST-Ca(II) are significantly cytotoxic to MC3T3 cells through a mechanism yet unknown; this is a potential problem to the biological utility of these complexes.« less

Cytotoxicity of Titanate-Calcium Complexes to MC3T3 Osteoblast-Like Cells

PubMed Central

Drury, Jeanie L.; Moussi, Joelle; Taylor-Pashow, Kathryn M. L.

2016-01-01

Monosodium titanates (MST) are a relatively novel form of particulate titanium dioxide that have been proposed for biological use as metal sorbents or delivery agents, most recently calcium (II). In these roles, the toxicity of the titanate or its metal complex is crucial to its biological utility. The aim of this study was to determine the cytotoxicity of MST and MST-calcium complexes with MC3T3 osteoblast-like cells; MST-Ca(II) complexes could be useful to promote bone formation in various hard tissue applications. MC3T3 cells were exposed to native MST or MST-Ca(II) complexes for 24–72 h. A CellTiter-Blue® assay was employed to assess the metabolic activity of the cells. The results showed that MST and MST-Ca(II) suppressed MC3T3 metabolic activity significantly in a dose-, time-, and cell-density-dependent fashion. MST-Ca(II) suppressed MC3T3 metabolism in a statistically identical manner as native MST at all concentrations. We concluded that MST and MST-Ca(II) are significantly cytotoxic to MC3T3 cells through a mechanism yet unknown; this is a potential problem to the biological utility of these complexes. PMID:28044136

Spectroscopic characterization and biological studies in vitro of a new silver complex with furosemide: Prospective of application as an antimicrobial agent

NASA Astrophysics Data System (ADS)

Lustri, Wilton R.; Lazarini, Silmara C.; Lustri, Bruna Cardinali; Corbi, Pedro P.; Silva, Maria Aline C.; Resende Nogueira, Flávia Aparecida; Aquino, Renata; Amaral, André C.; Treu Filho, Oswaldo; Massabni, Antonio Carlos; da Silva Barud, Hernane

2017-04-01

The present article describes the synthesis and biological studies in vitro of a novel silver complex with furosemide (Ag-FSE). Elemental, thermal and mass spectrometric analysis indicated a 1:1 metal/ligand composition, with the molecular formula AgC12H10ClN2O5S. Infrared and nuclear magnetic resonance studies suggest coordination of the ligand to the silver ion by the oxygen atoms of the carboxylate group. Additional Density Functional Theory (DFT) studies led to the proposition of the structure of the Ag-FSE complex. The antibacterial activities of the complex were primarily evaluated by antibiogram assays using the disc diffusion method and minimum inhibitory concentrations (MIC). Moreover, the mutagenicity of the complex was also evaluated to ensure that it is safe for subsequent application. The Ag-FSE complex has shown a significant in vitro antibacterial activity against Gram-positive Staphylococcus aureus (ATCC 25923), Gram negative Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853), and yeast Candida albicans (ATCC 90028). The absence of a mutagenic activity of Ag-FSE against Salmonella Typhimurium bacterial strains in the Ames assay is an extremely important finding for its future use as a drug in medicine.

Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro

PubMed Central

Leitmeyer, Katharina; Glutz, Andrea; Radojevic, Vesna; Setz, Cristian; Huerzeler, Nathan; Bumann, Helen; Bodmer, Daniel; Brand, Yves

2015-01-01

Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR) by blocking the mTOR complex 1 (mTORC1). mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However, less is known about the mTOR pathway in the inner ear. First, we evaluated whether or not the two mTOR complexes (mTORC1 and mTORC2, resp.) are present in the mammalian cochlea. Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzed in vitro. Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells. Moreover, spiral ganglion neurite number and length of neurites were significantly decreased in all concentrations used compared to control in a dose dependent manner. Our data indicate that the mTOR may play a role in the survival of hair cells and modulates spiral ganglion neuronal outgrowth and neurite formation. PMID:25918725

Application of a surfactant-assisted dispersive liquid-liquid microextraction method along with central composite design for micro-volume based spectrophotometric determination of low level of Cr(VI) ions in aquatic samples.

PubMed

Sobhi, Hamid Reza; Azadikhah, Efat; Behbahani, Mohammad; Esrafili, Ali; Ghambarian, Mahnaz

2018-05-09

A fast, simple, low cost surfactant-assisted dispersive liquid-liquid microextraction method along with central composite design for the determination of low level of Cr(VI) ions in several aquatic samples has been developed. Initially, Cr(VI) ions present in the aqueous sample were readily reacted with 1,5‑diphenylcarbazide (DPC) in acidic medium through complexation. Sodium dodecyl sulfate (SDS), as an anionic surfactant, was then employed as an ion-pair agent to convert the cationic complex into the neutral one. Following on, the whole aqueous phase underwent a dispersive liquid-liquid microextraction (DLLME) leading to the transfer of the neutral complex into the fine droplet of organic extraction phase. A micro-volume spectrophotometer was used to determine Cr(VI) concentrations. Under the optimized conditions predicted by the statistical design, the limit of quantification (LOQ) obtained was reported to be 5.0 μg/L, and the calibration curve was linear over the concentration range of 5-100 μg/L. Finally, the method was successfully implemented for the determination of low levels of Cr(VI) ions in various real aquatic samples and the accuracies fell within the range of 83-102%, while the precision varied in the span of 1.7-5.2%. Copyright © 2018. Published by Elsevier B.V.

Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro.

PubMed

Leitmeyer, Katharina; Glutz, Andrea; Radojevic, Vesna; Setz, Cristian; Huerzeler, Nathan; Bumann, Helen; Bodmer, Daniel; Brand, Yves

2015-01-01

Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR) by blocking the mTOR complex 1 (mTORC1). mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However, less is known about the mTOR pathway in the inner ear. First, we evaluated whether or not the two mTOR complexes (mTORC1 and mTORC2, resp.) are present in the mammalian cochlea. Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzed in vitro. Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells. Moreover, spiral ganglion neurite number and length of neurites were significantly decreased in all concentrations used compared to control in a dose dependent manner. Our data indicate that the mTOR may play a role in the survival of hair cells and modulates spiral ganglion neuronal outgrowth and neurite formation.

Complexing agent and heavy metal removals from metal plating effluent by electrocoagulation with stainless steel electrodes.

PubMed

Kabdaşli, Işik; Arslan, Tülin; Olmez-Hanci, Tuğba; Arslan-Alaton, Idil; Tünay, Olcay

2009-06-15

In the present study, the treatability of a metal plating wastewater containing complexed metals originating from the nickel and zinc plating process by electrocoagulation using stainless steel electrodes was experimentally investigated. The study focused on the effect of important operation parameters on electrocoagulation process performance in terms of organic complex former, nickel and zinc removals as well as sludge production and specific energy consumption. The results indicated that increasing the applied current density from 2.25 to 9.0 mA/cm(2) appreciably enhanced TOC removal efficiency from 20% to 66%, but a further increase in the applied current density to 56.25 mA/cm(2) did not accelerate TOC removal rates. Electrolyte concentration did not affect the process performance significantly and the highest TOC reduction (66%) accompanied with complete heavy metal removals were achieved at the original chloride content ( approximately 1500 mg Cl/L) of the wastewater sample. Nickel removal performance was adversely affected by the decrease of initial pH from its original value of 6. Optimum working conditions for electrocoagulation of metal plating effluent were established as follows: an applied current density of 9 mA/cm(2), the effluent's original electrolyte concentration and pH of the composite sample. TOC removal rates obtained for all electrocoagulation runs fitted pseudo-first-order kinetics very well (R(2)>92-99).

Determination of the concentrations of alternative antifouling agents on the Korean coast.

PubMed

Lee, Seongeon; Lee, Yong-Woo

2016-12-15

Since the ban on tributyltin (TBT) in 2008, dozens of alternative antifouling agents have been used instead. Unfortunately, these alternative antifouling agents contain diverse toxic components, which have contaminated the coasts. From 2006 to 2013, the concentration of chlorothalonil, dichlofluanid, and Irgarol 1051 were monitored continuously, and their mean concentrations increased due to the increase in maritime cargo and consequent increase in the incoming and outgoing ships in harbors. An analysis of the sampling points according to harbor type showed that the contamination was more severe in fishing and big harbors, where there are more incoming and outgoing ships. A correlation analysis indicated a high correlation between chlorothalonil and dichlofluanid. Unlike Irgarol 1051, which is only used as an antifouling agent, the other two substances are used as agricultural chemicals as well, which could explain the high correlation. This study suggests that these alternative antifouling agents should be tracked continuously. Copyright © 2016 Elsevier Ltd. All rights reserved.

Colloidal and electrochemical aspects of copper-CMP

NASA Astrophysics Data System (ADS)

Sun, Yuxia

Copper based interconnects with low dielectric constant layers are currently used to increase interconnect densities and reduce interconnect time delays in integrated circuits. The technology used to develop copper interconnects involves Chemical Mechanical Planarization (CMP) of copper films deposited on low-k layers (silica or silica based films), which is carried out using slurries containing abrasive particles. One issue using such a structure is copper contamination over dielectric layers (SiO2 film), if not reduced, this contamination will cause current leakage. In this study, the conditions conducive to copper contamination onto SiO2 films during Cu-CMP process were studied, and a post-CMP cleaning technique was discussed based on experimental results. It was found that the adsorption of copper onto a silica surface is kinetically fast (<0.5 minute). The amount of copper absorbed is pH and concentration dependent and affected by presence of H2O2, complexing agents, and copper corrosion inhibitor Benzotrazole. Based on de-sorption results, DI water alone was unable to reduce adsorbed copper to an acceptable level, especially for adsorption that takes place at a higher pH condition. The addition of complex agent, citric acid, proved effective in suppressing copper adsorption onto oxide silica during polishing or post-CMP cleaning by forming stable copper-CA complexes. Surface Complexation Modeling was used to simulate copper adsorption isotherms and predict the copper contamination levels on SiO2 surfaces. Another issue with the application of copper CMP is its environmental impact. CMP is a costly process due to its huge consumption of pure water and slurry. Additionally, Cu-CMP processing generates a waste stream containing certain amounts of copper and abrasive slurry particles. In this study, the separation technique electrocoagulation was investigated to remove both copper and abrasive slurry particles simultaneously. For effluent containing ˜40 ppm dissolved copper, it was found that ˜90% dissolved copper was removed from the waste streams through electroplating and in-situ chemical precipitation. The amount of copper removed through plating is impacted by membrane surface charge, type/amount of complexing agents, and solid content in the slurry suspension. The slurry particles can be removed ˜90% within 2 hours of EC through multiple mechanisms.

Integrating planning and reactive control

NASA Technical Reports Server (NTRS)

Wilkins, David E.; Myers, Karen L.

1994-01-01

Our research is developing persistent agents that can achieve complex tasks in dynamic and uncertain environments. We refer to such agents as taskable, reactive agents. An agent of this type requires a number of capabilities. The ability to execute complex tasks necessitates the use of strategic plans for accomplishing tasks; hence, the agent must be able to synthesize new plans at run time. The dynamic nature of the environment requires that the agent be able to deal with unpredictable changes in its world. As such, agents must be able to react to unanticipated events by taking appropriate actions in a timely manner, while continuing activities that support current goals. The unpredictability of the world could lead to failure of plans generated for individual tasks. Agents must have the ability to recover from failures by adapting their activities to the new situation, or replanning if the world changes sufficiently. Finally, the agent should be able to perform in the face of uncertainty. The Cypress system, described here, provides a framework for creating taskable, reactive agents. Several features distinguish our approach: (1) the generation and execution of complex plans with parallel actions; (2) the integration of goal-driven and event driven activities during execution; (3) the use of evidential reasoning for dealing with uncertainty; and (4) the use of replanning to handle run-time execution problems. Our model for a taskable, reactive agent has two main intelligent components, an executor and a planner. The two components share a library of possible actions that the system can take. The library encompasses a full range of action representations, including plans, planning operators, and executable procedures such as predefined standard operating procedures (SOP's). These three classes of actions span multiple levels of abstraction.

Integrating planning and reactive control

NASA Astrophysics Data System (ADS)

Wilkins, David E.; Myers, Karen L.

1994-10-01

Our research is developing persistent agents that can achieve complex tasks in dynamic and uncertain environments. We refer to such agents as taskable, reactive agents. An agent of this type requires a number of capabilities. The ability to execute complex tasks necessitates the use of strategic plans for accomplishing tasks; hence, the agent must be able to synthesize new plans at run time. The dynamic nature of the environment requires that the agent be able to deal with unpredictable changes in its world. As such, agents must be able to react to unanticipated events by taking appropriate actions in a timely manner, while continuing activities that support current goals. The unpredictability of the world could lead to failure of plans generated for individual tasks. Agents must have the ability to recover from failures by adapting their activities to the new situation, or replanning if the world changes sufficiently. Finally, the agent should be able to perform in the face of uncertainty. The Cypress system, described here, provides a framework for creating taskable, reactive agents. Several features distinguish our approach: (1) the generation and execution of complex plans with parallel actions; (2) the integration of goal-driven and event driven activities during execution; (3) the use of evidential reasoning for dealing with uncertainty; and (4) the use of replanning to handle run-time execution problems. Our model for a taskable, reactive agent has two main intelligent components, an executor and a planner. The two components share a library of possible actions that the system can take. The library encompasses a full range of action representations, including plans, planning operators, and executable procedures such as predefined standard operating procedures (SOP's). These three classes of actions span multiple levels of abstraction.

Determination of ultra-trace aluminum in human albumin by cloud point extraction and graphite furnace atomic absorption spectrometry.

PubMed

Sun, Mei; Wu, Qianghua

2010-04-15

A cloud point extraction (CPE) method for the preconcentration of ultra-trace aluminum in human albumin prior to its determination by graphite furnace atomic absorption spectrometry (GFAAS) had been developed in this paper. The CPE method was based on the complex of Al(III) with 1-(2-pyridylazo)-2-naphthol (PAN) and Triton X-114 was used as non-ionic surfactant. The main factors affecting cloud point extraction efficiency, such as pH of solution, concentration and kind of complexing agent, concentration of non-ionic surfactant, equilibration temperature and time, were investigated in detail. An enrichment factor of 34.8 was obtained for the preconcentration of Al(III) with 10 mL solution. Under the optimal conditions, the detection limit of Al(III) was 0.06 ng mL(-1). The relative standard deviation (n=7) of sample was 3.6%, values of recovery of aluminum were changed from 92.3% to 94.7% for three samples. This method is simple, accurate, sensitive and can be applied to the determination of ultra-trace aluminum in human albumin. 2009 Elsevier B.V. All rights reserved.

Separation of Molybdenum from Acidic High-Phosphorus Tungsten Solution by Solvent Extraction

NASA Astrophysics Data System (ADS)

Li, Yongli; Zhao, Zhongwei

2017-10-01

A solvent-extraction process for deep separation of molybdenum from an acidic high-phosphate tungsten solution was developed using tributyl phosphate (TBP) as the extractant and hydrogen peroxide (H2O2) as a complexing agent. The common aqueous complexes of tungsten and molybdenum (PMoxW12-xO40 3-, x = 0-12) are depolymerized to {PO4[Mo(O)2(O-O)]4}3- and {PO4[W(O)2(O-O)]4}3- by H2O2. The former can be preferentially extracted by TBP. The extractant concentration, phase contact time, H2O2 dosage, and H2SO4 concentration were optimized. By employing 80% by volume TBP, O:A = 1:1, 1.0 mol/L H2SO4, 1.0 mol/L H3PO4, a contact time of 2 min, and a molar ratio of H2O2/(W + Mo) equal to 1.5, 60.2% molybdenum was extracted in a single stage, while limiting tungsten co-extraction to 3.2%. An extraction isotherm indicated that the raffinate could be reduced to <0.1 g/L Mo in six stages of continuous counter-current extraction.

Biological control of wilt disease complex on tomato crop caused by Meloidogyne javanica and Fusarium oxysporum f.sp. lycopersici by Verticillium leptobactrum.

PubMed

Hajji-Hedfi, Lobna; Regaieg, Hajer; Larayedh, Asma; Chihani, Noura; Horrigue-Raouani, Najet

2017-09-23

The efficacy of Verticillium leptobactrum isolate (HR1) was evaluated in the control of root-knot nematode and Fusarium wilt fungus under laboratory and greenhouse conditions. Five concentrations of V. leptobactrum (HR1) isolate were tested for their nematicidal and fungicidal activities against Meloidogyne javanica and Fusarium oxysporum f.sp. lycopersici in vitro. Laboratory trials showed that mycelium growth inhibition of Fusarium wilt fungus was correlated to the increase of the concentration of culture filtrate. All dilutions showed efficiency in reducing the growth of Fusarium oxysporum f.sp. lycopersici. The greatest nematicidal activity was observed at 50, 75, and 100% filtrate dilutions. The egg hatching percentage reached 42%, and the juvenile's corrected mortality registered 90% for the above treatments. In greenhouse experiment, the biocontrol agent fungus enhanced significantly tomato growth components (height and weight of plant and root). The multiplication rate of root-knot nematode and the Fusarium wilt disease incidence declined significantly with soil application of V. leptobactrum as with chemical treatments. The isolate HR1 was efficient to control wilt disease complex caused by M. javanica and Fusarium oxysporum f.sp. lycopersici.

Brief introductory guide to agent-based modeling and an illustration from urban health research.

PubMed

Auchincloss, Amy H; Garcia, Leandro Martin Totaro

2015-11-01

There is growing interest among urban health researchers in addressing complex problems using conceptual and computation models from the field of complex systems. Agent-based modeling (ABM) is one computational modeling tool that has received a lot of interest. However, many researchers remain unfamiliar with developing and carrying out an ABM, hindering the understanding and application of it. This paper first presents a brief introductory guide to carrying out a simple agent-based model. Then, the method is illustrated by discussing a previously developed agent-based model, which explored inequalities in diet in the context of urban residential segregation.

Brief introductory guide to agent-based modeling and an illustration from urban health research

PubMed Central

Auchincloss, Amy H.; Garcia, Leandro Martin Totaro

2017-01-01

There is growing interest among urban health researchers in addressing complex problems using conceptual and computation models from the field of complex systems. Agent-based modeling (ABM) is one computational modeling tool that has received a lot of interest. However, many researchers remain unfamiliar with developing and carrying out an ABM, hindering the understanding and application of it. This paper first presents a brief introductory guide to carrying out a simple agent-based model. Then, the method is illustrated by discussing a previously developed agent-based model, which explored inequalities in diet in the context of urban residential segregation. PMID:26648364

Synthesis of DTPA analogues derived from piperidine and azepane: potential contrast enhancement agents for magnetic resonance imaging.

PubMed

Chong, H S; Garmestani, K; Bryant, L H; Brechbiel, M W

2001-11-16

Two DTPA derivatives (PIP-DTPA and AZEP-DTPA) as potential contrast enhancement agents in MRI are synthesized. The T1 and T2 relaxivities of their corresponding Gd(III) complexes are reported. At clinically relevant field strengths, the relaxivities of the complexes are comparable to that of the contrast agent, Gd(DTPA) which is in clinical use. The serum stability of the (153)Gd-labeled complexes is assessed by measuring the release of (153)Gd from the ligands. The radiolabeled Gd chelates are found to be kinetically stable in human serum for up to at least 14 days without any measurable loss of radioactivity.

REGULATORY MECHANISMS OF CELLULAR RESPIRATION

PubMed Central

Barron, E. S. Guzman; Nelson, Leonard; Ardao, Maria Isabel

1948-01-01

Oxidizing agents of sulfhydryl groups such as iodosobenzoate, alkylating agents such as iodoacetamide, and mercaptide-forming agents such as cadmium chloride, mercuric chloride, p-chloromercuribenzoate, sodium arsenite, and p-carboxyphenylarsine oxide, added in small concentrations to a suspension of sea urchin sperm produced an increase in respiration. When the concentration was increased there was an inhibition. These effects are explained by postulating the presence in the cells of two kinds of sulfhydryl groups: soluble sulfhydryl groups, which regulate cellular respiration, and fixed sulfhydryl groups, present in the protein moiety of enzymes. Small concentrations of sulfhydryl reagents combine only with the first, thus producing an increase in respiration; when the concentration is increased, the fixed sulfhydryl groups are also attacked and inhibition of respiration is the consequence. Other inhibitors of cell respiration, such as cyanide and urethanes, which do not combine with —SH groups, did not stimulate respiration in small concentration. PMID:18891144

Quantitative detection of pathogens in centrifugal microfluidic disks

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

Koh, Chung-Yan; Schaff, Ulrich Y.; Sommer, Gregory Jon

A system and methods for detection of a nucleic acid including forming a plurality of nucleic acid detection complexes are described, each of the complexes including a nucleic acid analyte, a detection agent and a functionalized probe. The method further including binding the nucleic acid detection complexes to a plurality of functionalized particles in a fluid sample and separating the functionalized particles having the nucleic acid detection complexes bound thereto from the fluid sample using a density media. The nucleic acid analyte is detected by detecting the detection agent.

Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

PubMed

Sun, Jihong; Zhang, Shizheng; Jiang, Shaojie; Bai, Weixian; Liu, Fei; Yuan, Hong; Ji, Jiansong; Luo, Jingfeng; Han, Guocan; Chen, Lumin; Jin, Yin; Hu, Peng; Yu, Lei; Yang, Xiaoming

2016-09-01

Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

Genetic diversity-independent neutralization of pandemic viruses (e.g. HIV), potentially pandemic (e.g. H5N1 strain of influenza) and carcinogenic (e.g. HBV and HCV) viruses and possible agents of bioterrorism (variola) by enveloped virus neutralizing compounds (EVNCs).

PubMed

Kotwal, Girish J

2008-06-06

Genetic diversity and hypermutation contribute to difficulties in developing a vaccine against viruses like HIV and influenza. There are currently no known immune correlates of protection against HIV. This has made the development of a vaccine against HIV that would provide sterilizing immunity in the near future an impossible task. The abandonment of a recent AIDS vaccine human trial due to a failure to elicit a protective sterilising immune response confirms that empirical attempts to develop a vaccine may result in failures. Also the difficulty in predicting the next pandemic strain of influenza may make it difficult to respond rapidly should there be an outbreak. Therefore, it is time to explore broad spectrum agents that can target either the lipid portion of the envelope or the sugar moieties of the glycoproteins or the rafts (regions within viral and cell envelopes where a higher concentration of the glycoproteins exist). Broad spectrum agents that can serve as disrafters or neutralize the viral infectivity by binding to the envelope lipid or sugar moieties will not be affected by the vagaries of hypermutation of surface antigens. This is because the post-translation modification is a host function. Presented here is a review of recently reported agents present in pomegranate juice (polyphenols, beta-sitosterol, sugars and ellagic acid) and fulvic acid, described here as the envelope virus neutralising compounds (EVNCs) and complex molecules like lectins and mucins. Pomegranate juice was previously reported to inactivate HIV and further shown by our group to inactivate influenza, herpes viruses and poxviruses. A formulation consisting of fulvic acid, a complex mixture of compounds was previously reported to render vaccinia virus, HIV and SARS virus non-infectious. Recently, both fulvic acid and pomegranate juice have been shown to inactivate genetically diverse strains of influenza including H5N1, further confirming the broad spectrum nature of these agents. How EVNCs will be used in developing a vaccine achieving sterilizing immunity or prophylaxis needs to be researched.

Activities of E1210 and comparator agents tested by CLSI and EUCAST broth microdilution methods against Fusarium and Scedosporium species identified using molecular methods.

PubMed

Castanheira, Mariana; Duncanson, Frederick P; Diekema, Daniel J; Guarro, Josep; Jones, Ronald N; Pfaller, Michael A

2012-01-01

Fusarium (n = 67) and Scedosporium (n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum, 7 Scedosporium aurantiacum, and 28 Scedosporium prolificans species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC(90) values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, >16, >16, >8, >8, 8, and 4 μg/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC(90) was 0.12 μg/ml for S. apiospermum, but 1 to >8 μg/ml for other tested agents. Against S. aurantiacum, the MEC(50) for E1210 was 0.06 μg/ml versus 0.5 to >8 μg/ml for the comparators. Against S. prolificans, the MEC(90) for E1210 was only 0.12 μg/ml, compared to >4 μg/ml for amphotericin B and >8 μg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; ±2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and F. oxysporum species complex (SC) (60%), posaconazole and S. aurantiacum (85.7%), and voriconazole and S. aurantiacum (85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results.

Activities of E1210 and Comparator Agents Tested by CLSI and EUCAST Broth Microdilution Methods against Fusarium and Scedosporium Species Identified Using Molecular Methods

PubMed Central

Duncanson, Frederick P.; Diekema, Daniel J.; Guarro, Josep; Jones, Ronald N.; Pfaller, Michael A.

2012-01-01

Fusarium (n = 67) and Scedosporium (n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum, 7 Scedosporium aurantiacum, and 28 Scedosporium prolificans species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC90 values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, >16, >16, >8, >8, 8, and 4 μg/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC90 was 0.12 μg/ml for S. apiospermum, but 1 to >8 μg/ml for other tested agents. Against S. aurantiacum, the MEC50 for E1210 was 0.06 μg/ml versus 0.5 to >8 μg/ml for the comparators. Against S. prolificans, the MEC90 for E1210 was only 0.12 μg/ml, compared to >4 μg/ml for amphotericin B and >8 μg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; ±2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and F. oxysporum species complex (SC) (60%), posaconazole and S. aurantiacum (85.7%), and voriconazole and S. aurantiacum (85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results. PMID:22083469

Hydroxypyridonate and hydroxypyrimidinone chelating agents

DOEpatents

Raymond, Kenneth N.; Doble, Daniel M.; Sunderland, Christopher J.; Thompson, Marlon

2005-01-25

The present invention provides hydroxypyridinone and hydroxypyrimidone chelating agents. Also provides are Gd(III) complexes of these agents, which are useful as contrast enhancing agents for magnetic resonance imaging. The invention also provides methods of preparing the compounds of the invention, as well as methods of using the compounds in magnetic resonance imaging applications.

Market-Based Coordination and Auditing Mechanisms for Self-Interested Multi-Robot Systems

ERIC Educational Resources Information Center

Ham, MyungJoo

2009-01-01

We propose market-based coordinated task allocation mechanisms, which allocate complex tasks that require synchronized and collaborated services of multiple robot agents to robot agents, and an auditing mechanism, which ensures proper behaviors of robot agents by verifying inter-agent activities, for self-interested, fully-distributed, and…

Improved Dye Stability in Single-Molecule Fluorescence Experiments

NASA Astrophysics Data System (ADS)

EcheverrÍa Aitken, Colin; Marshall, R. Andrew; Pugi, Joseph D.

Complex biological systems challenge existing single-molecule methods. In particular, dye stability limits observation time in singlemolecule fluorescence applications. Current approaches to improving dye performance involve the addition of enzymatic oxygen scavenging systems and small molecule additives. We present an enzymatic oxygen scavenging system that improves dye stability in single-molecule experiments. Compared to the currently-employed glucose-oxidase/catalase system, the protocatechuate-3,4-dioxygenase system achieves lower dissolved oxygen concentration and stabilizes single Cy3, Cy5, and Alexa488 fluorophores. Moreover, this system possesses none of the limitations associated with the glucose oxidase/catalase system. We also tested the effects of small molecule additives in this system. Biological reducing agents significantly destabilize the Cy5 fluorophore as a function of reducing potential. In contrast, anti-oxidants stabilize the Cy3 and Alexa488 fluorophores. We recommend use of the protocatechuate-3,4,-dioxygenase system with antioxidant additives, and in the absence of biological reducing agents. This system should have wide application to single-molecule fluorescence experiments.

Facile fabrication of high-quality Ag/PS coaxial nanocables based on the mixed mode of soft/hard templates

PubMed Central

Wan, Mimi; Zhao, Wenbo; Peng, Fang; Wang, Qi; Xu, Ping; Mao, Chun; Shen, Jian

2016-01-01

A new kind of high-quality Ag/PS coaxial nanocables can be facilely synthesized by using soft/hard templates method. In order to effectively introduce Ag sources into porous polystyrene (PS) nanotubes which were trapped in porous anodic aluminum oxide (AAO) hard template, Pluronic F127 (F127) was used as guiding agent, soft template and reductant. Meanwhile, ethylene glycol solution was also used as solvent and co-reducing agent to assist in the formation of silver nanowires. The influences of concentration of F127 and reducing reaction time on the formation of Ag/PS coaxial nanocables were discussed. Results indicated that the high-quality Ag/PS coaxial nanocables can be obtained by the mixed mode of soft/hard templates under optimized conditions. This strategy is expected to be extended to design more metal/polymer coaxial nanocables for the benefit of creation of complex and functional nanoarchitectures and components. PMID:27477888

Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum

PubMed Central

Chiang, Annette N.; Valderramos, Juan-Carlos; Balachandran, Raghavan; Chovatiya, Raj J.; Mead, Brian P.; Schneider, Corinne; Bell, Samantha L.; Klein, Michael G.; Huryn, Donna M.; Chen, Xiaojiang S.; Day, Billy W.; Fidock, David A.; Wipf, Peter; Brodsky, Jeffrey L.

2009-01-01

Plasmodium falciparum, the Apicomplexan parasite that is responsible for the most lethal forms of human malaria, is exposed to radically different environments and stress factors during its complex lifecycle. In any organism, Hsp70 chaperones are typically associated with tolerance to stress. We therefore reasoned that inhibition of P. falciparum Hsp70 chaperones would adversely affect parasite homeostasis. To test this hypothesis, we measured whether pyrimidinone-amides, a new class of Hsp70 modulators, could inhibit the replication of the pathogenic P. falciparum stages in human red blood cells. Nine compounds with IC50 values from 30 nM to 1.6 μM were identified. Each compound also altered the ATPase activity of purified P. falciparum Hsp70 in single-turnover assays, although higher concentrations of agents were required than was necessary to inhibit P. falciparum replication. Varying effects of these compounds on Hsp70s from other organisms were also observed. Together, our data indicate that pyrimidinone-amides constitute a novel class of anti-malarial agents. PMID:19195901

Impact of Absorption and Transport on Intelligent Therapeutics and Nano-scale Delivery of Protein Therapeutic Agents

PubMed Central

Peppas, Nicholas A.; Carr, Daniel A

2009-01-01

The combination of materials design and advances in nanotechnology has led to the development of new therapeutic protein delivery systems. The pulmonary, nasal, buccal and other routes have been investigated as delivery options for protein therapy, but none result in improved patient compliances and patient quality of life as the oral route. For the oral administration of these new systems, an understanding of protein transport is essential because of the dynamic nature of the gastrointestinal tract and the barriers to transport that exist. Models have been developed to describe the transport between the gastrointestinal lumen and the bloodstream, and laboratory techniques like cell culture provide a means to investigate the absorption and transport of many therapeutic agents. Biomaterials, including stimuli-sensitive complexation hydrogels, have been investigated as promising carriers for oral delivery. However, the need to develop models that accurately predict protein blood concentration as a function of the material structure and properties still exists. PMID:20161384

Influence of Mycotoxins and a Mycotoxin Adsorbing Agent on the Oral Bioavailability of Commonly Used Antibiotics in Pigs

PubMed Central

Goossens, Joline; Vandenbroucke, Virginie; Pasmans, Frank; De Baere, Siegrid; Devreese, Mathias; Osselaere, Ann; Verbrugghe, Elin; Haesebrouck, Freddy; De Saeger, Sarah; Eeckhout, Mia; Audenaert, Kris; Haesaert, Geert; De Backer, Patrick; Croubels, Siska

2012-01-01

It is recognized that mycotoxins can cause a variety of adverse health effects in animals, including altered gastrointestinal barrier function. It is the aim of the present study to determine whether mycotoxin-contaminated diets can alter the oral bioavailability of the antibiotics doxycycline and paromomycin in pigs, and whether a mycotoxin adsorbing agent included into diets interacts with those antibiotics. Experiments were conducted with pigs utilizing diets that contained blank feed, mycotoxin-contaminated feed (T-2 toxin or deoxynivalenol), mycotoxin-contaminated feed supplemented with a glucomannan mycotoxin binder, or blank feed supplemented with mycotoxin binder. Diets with T-2 toxin and binder or deoxynivalenol and binder induced increased plasma concentrations of doxycycline administered as single bolus in pigs compared to diets containing blank feed. These results suggest that complex interactions may occur between mycotoxins, mycotoxin binders, and antibiotics which could alter antibiotic bioavailability. This could have consequences for animal toxicity, withdrawal time for oral antibiotics, or public health. PMID:22606377

Epigenetic Modifications in Essential Hypertension

PubMed Central

Wise, Ingrid A.; Charchar, Fadi J.

2016-01-01

Essential hypertension (EH) is a complex, polygenic condition with no single causative agent. Despite advances in our understanding of the pathophysiology of EH, hypertension remains one of the world’s leading public health problems. Furthermore, there is increasing evidence that epigenetic modifications are as important as genetic predisposition in the development of EH. Indeed, a complex and interactive genetic and environmental system exists to determine an individual’s risk of EH. Epigenetics refers to all heritable changes to the regulation of gene expression as well as chromatin remodelling, without involvement of nucleotide sequence changes. Epigenetic modification is recognized as an essential process in biology, but is now being investigated for its role in the development of specific pathologic conditions, including EH. Epigenetic research will provide insights into the pathogenesis of blood pressure regulation that cannot be explained by classic Mendelian inheritance. This review concentrates on epigenetic modifications to DNA structure, including the influence of non-coding RNAs on hypertension development. PMID:27023534

Low level chemiluminescence from liquid culture media.

PubMed

Vogel, R; Süssmuth, R

1999-06-01

Low level chemiluminescence (CL) can be observed from autoclaved liquid culture media, as used in microbiology. The light emission is oxygen-dependent and arises from reactions following auto-oxidation of reducing Maillard products which are formed during autoclaving. The inhibition of this CL by radical scavengers and antioxidants has been studied. As superoxide radicals and hydrogen peroxide are predominantly involved in the initiation of the CL, the investigation of CL from culture media offers a convenient tool for the detection of exogenous (medium-mediated) oxidative stress being imposed onto micro-organisms in culture. Transition metal ions showed, dependent on concentration, both inhibitory and stimulating effects on the CL, which was also affected by the presence of complexing agents. Iron porphyrins and related complexes displayed a very efficient quenching of the CL, which may be of particular importance, as aerobic micro-organisms have been previously shown to be very efficient in quenching the CL from culture media.

Growth stimulation of Porphyromonas endodontalis by hemoglobin and protoporphyrin IX.

PubMed

Zerr, M A; Cox, C D; Johnson, W T; Drake, D R

2000-12-01

Porphyromonas endodontalis, like other Porphyromonas species, has a complex set of nutritional requirements. In addition to being an obligate anaerobe, the bacterium must be grown in a complex medium consisting of amino acids, reducing agents and heme compounds. P. endodontalis accumulates high concentrations of heme pigments to the extent that colonies appear black on blood agar. This accumulation of heme and the need for these compounds has been characterized as iron requirements by these species. However, in our studies, P. endodontalis demonstrated growth dependence on hemoglobin or protoporphyrin IX but not on free iron. Iron added to other heme compounds actually decreased growth stimulation by porphyrin-containing compounds. P. endodontalis actively transported free iron, but this process did not appear to be critical for growth. The maximum stimulation of growth by protoporphyrin IX, under conditions of iron deprivation, suggests that P. endodontalis requires the porphyrin moiety as a growth factor.

Comparative studies of the influence of cyclodextrins on the stability of the sunscreen agent, 2-ethylhexyl-p-methoxycinnamate.

PubMed

Scalia, Santo; Casolari, Alberto; Iaconinoto, Antonietta; Simeoni, Silvia

2002-11-07

The effects of beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the base-catalyzed degradation and light-induced decomposition of the sunscreen agent, trans-2-ethylhexyl-p-methoxycinnamate (trans-EHMC) were investigated. Reversed-phase liquid chromatography was used to study the interaction between natural and modified cyclodextrins, added to the mobile phase, and the sunscreen. Among the available cyclodextrins (beta-CD, HP-beta-CD, hydroxypropyl-alpha-cyclodextrin and hydroxypropyl-gamma-cyclodextrin), only HP-beta-CD and beta-CD produced a significant decrease in the chromatographic retention of trans-EHMC. The complexation of the sunscreen agent with HP-beta-CD and beta-CD was confirmed by thermal analysis and nuclear magnetic resonance spectroscopy. beta-CD depressed the decomposition of trans-EHMC in alkaline solutions more effectively than HP-beta-CD. Moreover, the irradiation-induced degradation of the sunscreen agent in emulsion vehicles was reduced by complexation with beta-CD (the extent of degradation was 26.1% for the complex compared to 35.8% for free trans-EHMC) whereas HP-beta-CD had no significant effect. Therefore, the complex of beta-CD with trans-EHMC enhances the chemical- and photo-stability of the sunscreen agent. Moreover, it limits adverse interactions of the UV filter with other formulation ingredients.

Syntheses, Characterization, Resolution, and Biological Studies of Coordination Compounds of Aspartic Acid and Glycine

PubMed Central

Akinkunmi, Ezekiel; Ojo, Isaac; Adebajo, Clement; Isabirye, David

2017-01-01

Enantiomerically enriched coordination compounds of aspartic acid and racemic mixtures of coordination compounds of glycine metal-ligand ratio 1 : 3 were synthesized and characterized using infrared and UV-Vis spectrophotometric techniques and magnetic susceptibility measurements. Five of the complexes were resolved using (+)-cis-dichlorobis(ethylenediamine)cobalt(III) chloride, (+)-bis(glycinato)(1,10-phenanthroline)cobalt(III) chloride, and (+)-tris(1,10-phenanthroline)nickel(II) chloride as resolving agents. The antimicrobial and cytotoxic activities of these complexes were then determined. The results obtained indicated that aspartic acid and glycine coordinated in a bidentate fashion. The enantiomeric purity of the compounds was in the range of 22.10–32.10%, with (+)-cis-dichlorobis(ethylenediamine)cobalt(III) complex as the more efficient resolving agent. The resolved complexes exhibited better activity in some cases compared to the parent complexes for both biological activities. It was therefore inferred that although the increase in the lipophilicity of the complexes may assist in the permeability of the complexes through the cell membrane of the pathogens, the enantiomeric purity of the complexes is also of importance in their activity as antimicrobial and cytotoxic agents. PMID:28293149

Quantitative imaging of intracellular signaling for personalized pancreatic cancer therapy in an in vivo avatar (Conference Presentation)

NASA Astrophysics Data System (ADS)

Samkoe, Kimberley S.; Schultz, Emily; Park, Yeonjae; Fischer, Dawn; Pogue, Brian W.; Smith, Kerrington; Tichauer, Kenneth M.; Gibbs, Summer L.

2017-02-01

Pancreatic ductal adenocarcinomas (PDAC) are notoriously difficult to treat and in general, molecular targeted therapies have failed even when the targeted protein is overexpressed in the tumor tissue. Genetic mutations in extracellular receptors and downstream signaling proteins (i.e., RAS signaling pathway) and convoluted intracellular cross-talk between cell signaling pathways are likely reasons that these promising therapies fail. Monitoring the complex relationship between intracellular protein signaling is difficult and to-date, standard techniques that are used (Western blot, flow cytometry, immunohistochemistry, etc.) are invasive, static and do not accurately represent in vivo structure-function relationships. Here, we describe the development of an in ovo avatar using patient derived tumors grown on the chicken chorioallantoic membrane (CAM) and the novel fluorescence-based Quantitative Protein Expression Tracking (QUIET) methodology to bridge the gap between oncology, genomics and patient outcomes. Previously developed paired-agent imaging, was extended to a three-compartment model system in QUIET, which utilizes three types of imaging agents: novel fluorophore conjugated cell permeable targeted and untargeted small molecule paired-agents, in addition to a tumor perfusion agent that is not cell membrane permeable. We have demonstrated the ability to quantify the intracellular binding domain of a trans-membrane protein in vitro using cell permeable fluorescent agents (erlotinib-TRITC and control isotype-BODIPY FL). In addition, we have demonstrated imaging protocols to simultaneously image up to 6 spectrally distinct organic fluorophores in in ovo avatars using the Nuance EX (Perkin Elmer) and established proof-of-principle intracellular and extracellular protein concentrations of epidermal growth factor receptor using QUIET and traditional paired-agent imaging.

Paired-agent imaging for resection during surgery (PAIRS) of head and neck squamous cell carcinomas (Conference Presentation)

NASA Astrophysics Data System (ADS)

Samkoe, Kimberley S.; Tichauer, Kenneth M.; Chen, Eunice; Gunn, Jason R.; Hoopes, P. Jack; Wells, Wendy A.; Hasan, Tayyaba; Pogue, Brian W.

2016-03-01

Ninety percent of patients with head and neck squamous cell carcinomas (HNSCC) have overexpression of epidermal growth factor receptor (EGFR), which is correlated with poor prognosis. Complete surgical resection of HNSCC tumors has a large impact on patient survival, where detection of tumor at or close to surgical margins increases the risk of death at 5-years by 90%. In addition, large surgical margins can greatly increase the morbidity experienced by the patient due to functional and cosmetic damage of oral and facial structures. Single fluorescence targeting agents are often used for tumor detection in in vivo pre-clinical imaging; however, the arising signal is qualitative at best because it is a complex mixture of vascular perfusion, vascular leakage, inhibited lymphatic clearance, and receptor binding. In vivo ratiometric receptor concentration imaging (RCI) allows quantification of receptor expression (hence identification of cancerous tissue) by utilizing co-administered paired-agents consisting of a targeted agent and non-targeted perfusion agent to reference the plasma delivery and leakage. A panel of HNSCC tumors with varying levels of EGFR expression (SCC-15 >SCC-25 > SCC-09) have been imaged using ABY-029, a clinically relevant anti-EGFR affibody labeled with IRDye 800CW, and affibody control imaging agent labeled with IRDye 680RD. RCI maps of in vivo tissue have been created and are spatially correlated with EGFR and CD31 immunohistochemistry and basic H and E staining. The RCI threshold parameters for distinguishing tumor from normal tissues (skin and muscle) and the accuracy of margin detection in these tumors will be presented. RCI surgical resection will be further developed using a novel multi-channel, gated fluorescence-guided surgery (FGS) imaging system that is capable of performing RCI in normal room light.

The development of GADD45α luciferase reporter assays in human cells for assessing the genotoxicity of environmental pollutants.

PubMed

Xin, Lili; Wang, Jianshu; Wu, Yanhu; Guo, Sifan

2015-02-01

In order to assess the potential carcinogenic and genotoxic responses induced by environmental pollutants, genotoxicity test systems based on a GADD45α promoter-driven luciferase reporter in human A549 and HepG2 cells were established. Four different types of environmental toxicants including DNA alkylating agents, precarcinogenic agents, DNA cross-linking agents and non-carcinogenic agents, and three environmental samples collected from a coke oven plant were used to evaluate the test systems. After treated with the tested agents and environmental samples for 12 h, the cell viabilities and luciferase activities of the luciferase reporter cells were determined, respectively. Methyl methanesulfonate, benzo[a]pyrene, formaldehyde and the extractable organic matter (EOM) from coke oven emissions in ambient air generally produced significant induction of relative luciferase activity in a similar dose-dependent manner in A549- and HepG2-luciferase cells. No significant increases in relative luciferase activity were observed in pyrene-treated A549- or HepG2-luciferase cells. Significant increase in relative luciferase activity was already evident after 2.5 µM benzo[a]pyrene, 5 µM formaldehyde, 0.006 µg/L bottom-EOM, 0.10 µg/L side-EOM or 0.06 µg/L top-EOM, where no cytotoxic damage was observed. Compared with the A549-luciferase cells, the tested pollutants produced higher induction of relative luciferase activity in HepG2-luciferase cells. Therefore, the new genotoxicity test systems can detect different types of genotoxic agents and low concentrations of environmental samples. The luciferase reporter cells, especially the HepG2-luciferase cells, could provide a valuable tool for rapid screening of the genotoxic damage of environmental pollutants and their complex mixtures.

Drilling fluids and thinners therefor

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

Allison, G.M. III

1986-10-21

This patent describes an aqueous drilling fluid comprising water, finely divided solids and a first agent and a second agent. The first agent comprises a sulfoalkylated tannin containing no complexing heavy metal. The second agent comprises at least one at least partly water-soluble metal compound comprising tin. The weight ratio of the first agent to the second agent is in the range from about 100;1 to about 1:1.

Examination of water spray airborne coal dust capture with three wetting agents

PubMed Central

Organiscak, J.A.

2015-01-01

Water spray applications are one of the principal means of controlling airborne respirable dust in coal mines. Since many coals are hydrophobic and not easily wetted by water, wetting agents can be added to the spray water in an effort to improve coal wetting and assist with dust capture. In order to study wetting agent effects on coal dust capture, laboratory experiments were conducted with three wetting agents used by the coal industry on -325 mesh sized Pocahontas No. 3 coal dust. Significant differences in coal dust sink times were observed among the three wetting agents at water mixture concentrations of 0.05%, 0.1% and 0.2%. The best wetting agent as identified by the coal dust sink test was only tested at the lowest 0.05% water mixture concentration and was found to have a negligible effect on spray airborne dust capture. Water spray airborne dust capture results for all three wetting agents tested at a 0.2% water mixture concentration showed that all three wetting agents exhibit similar but small improvements in dust capture efficiency as compared with water. These results indicate that the coal dust sink test may not be a good predictor for the capture of airborne dust. Additional research is needed to examine if the coal dust sink test is a better predictor of wetting agent dust suppression effects during cutting, loading, conveying and dumping of coal products by comparison to airborne dust capture from sprays. PMID:26251565

Understanding aquatic animal virus survival and trafficking and its role in risk assessment

USGS Publications Warehouse

LaPatra, S.; Troyer, R.; Shewmaker, W.; Jones, G.; Kurath, Gael; Rogers, C.J.

2001-01-01

The stability of infectious agents in different media and under different physical and chemical environments has been extensively studied for some viruses and virtually ignored for others. Gaps in our knowledge are due in part to difficulties in reproducing virus «life cycles» and determination if the agent is in fact inactive. Additionally, isolation of the agent under certain conditions can present significant challenges. Studies on the susceptibility of viruses to different physical or chemical parameters have often been conducted under artificial conditions and quantitative data on the rate of inactivation are lacking for many agents. Using infectious hematopoietic necrosis virus (IHNV) as an example, survival was assessed under different environmental conditions. Three IHNV isolates that exhibited antigenic and genetic differences were diluted either in freshwater collected from a spring, after it passed through a fish farm, or the river that received water from the fish farm. Each treatment was incubated at 15o C in a water bath and samples were removed daily. Virus concentrations were determined by plaque assay on EPC cells. Virus suspended in spring water survived longer than virus incubated in water obtained from a fish farm or the river. Virus suspended in river water exhibited a 99.99% reduction in virus concentrations in less than 24 h. Survival of IHNV was also evaluated at different temperatures. A 1982 isolate appeared to be less temperature sensitive than isolates collected in 1990. A preliminary study was also conducted to determine the genetic similarity of IHNV isolates present downstream in a river system from the state of Idaho. Isolates were analyzed using the RNase protection assay (RPA) and by nucleotide sequencing of RT-PCR products of specific isolates. Genetic typing of IHNV allows monitoring of virus traffic and may provide insight into the epizootiology and mechanisms of virus spread. These results illustrate the complexity in evaluating virus survival and trafficing and using this sort of information in risk assessment.

Steady-state currents in p-n junction filaments or grains in case of large surface recombination velocities at lateral surfaces

NASA Technical Reports Server (NTRS)

Von Roos, O.; Lindholm, F. A.

1985-01-01

Recently it has been pointed out that the saturation current of a semiconductor filament which constitutes part of a p-n junction diverges when the surface recombination velocity at the faces become infinitely large. Here it is pointed out that this is to be expected on physical grounds since, whenever the carrier concentration is kept off equilibrium by an outside agent, and at the same time recombination lifetimes in the bulk or in surface layers tend to zero, concentration gradients tend to infinity. As also previously noted, the situation can be remedied by using realistic (finite) surface recombination velocities in model calculations. However, this procedure leads to mathematical complexities which have been circumvented recently by the introduction of a heuristic approach. It is the aim of this paper to assess the validity of the heuristic approach by means of detailed and exact calculations.

Agent-Based Models in Social Physics

NASA Astrophysics Data System (ADS)

Quang, Le Anh; Jung, Nam; Cho, Eun Sung; Choi, Jae Han; Lee, Jae Woo

2018-06-01

We review the agent-based models (ABM) on social physics including econophysics. The ABM consists of agent, system space, and external environment. The agent is autonomous and decides his/her behavior by interacting with the neighbors or the external environment with the rules of behavior. Agents are irrational because they have only limited information when they make decisions. They adapt using learning from past memories. Agents have various attributes and are heterogeneous. ABM is a non-equilibrium complex system that exhibits various emergence phenomena. The social complexity ABM describes human behavioral characteristics. In ABMs of econophysics, we introduce the Sugarscape model and the artificial market models. We review minority games and majority games in ABMs of game theory. Social flow ABM introduces crowding, evacuation, traffic congestion, and pedestrian dynamics. We also review ABM for opinion dynamics and voter model. We discuss features and advantages and disadvantages of Netlogo, Repast, Swarm, and Mason, which are representative platforms for implementing ABM.

Highly stabilized gadolinium chelates functionalized on metal nanoparticles as magnetic resonance imaging contrast agent

NASA Astrophysics Data System (ADS)

Siddiqui, Talha S.

Magnetic resonance imaging (MRI) is a non-invasive method for imaging and diagnosing tissue damage, organ function and the vascular system. Magnevist(TM) a complex of diethylenetriaminepentaacetic acid (DTPA) and Gd3+ is a clinically approved contrast agent for MRI. A derivative of DTPA was formed by the addition of two cysteine groups (DTPA-L-Cys) through amide linkage. The Gd complex of this ligand bonds with the silver surfaces through the cysteine thiols. GdDTPA-L-Cys was bound to ˜10nm diameter Ag nanoparticles for use as a multifunctional MRI contrast agent. The ligand and complex were characterized by 1H and 13C NMR, ESI-MS and IR spectroscopy. The silver construct was characterized by TEM, TGA and UV-Vis absorption spectra. The per metal complex r1 relaxivity of GdDTPA-L-Cys{Ag} greater than that of Magnavist(TM) with the same molarity for both compounds. The synthesis of a DTPA derivative is described that allows it to bind to silver or gold nanoparticles through a single thiol linkage (DTPASH). The resulting Gd complex, GdDTPASH, was bound to Ag nanoparticles to create a single monolayer on the surface. The construct was further stabilized in buffered solution with the addition of a thiolated PEG chain. The highly stabilized nanoparticle construct delivers a high payload of Gd compelex and is an effective T1 brightening agent. The production of this type of construct opens the way for engineered multimodal MRI contrast agents.

Implications of complex adaptive systems theory for interpreting research about health care organizations.

PubMed

Jordon, Michelle; Lanham, Holly Jordan; Anderson, Ruth A; McDaniel, Reuben R

2010-02-01

Data about health care organizations (HCOs) are not useful until they are interpreted. Such interpretations are influenced by the theoretical lenses used by the researcher. Our purpose was to suggest the usefulness of theories of complex adaptive systems (CASs) in guiding research interpretation. Specifically, we addressed two questions: (1) What are the implications for interpreting research observations in HCOs of the fact that we are observing relationships among diverse agents? (2) What are the implications for interpreting research observations in HCOs of the fact that we are observing relationships among agents that learn? We defined diversity and learning and the implications of the non-linear relationships among agents from a CAS perspective. We then identified some common analytical practices that were problematic and may lead to conceptual and methodological errors. Then we described strategies for interpreting the results of research observations. We suggest that the task of interpreting research observations of HCOs could be improved if researchers take into account that the systems they study are CASs with non-linear relationships among diverse, learning agents. Our analysis points out how interpretation of research results might be shaped by the fact that HCOs are CASs. We described how learning is, in fact, the result of interactions among diverse agents and that learning can, by itself, reduce or increase agent diversity. We encouraged researchers to be persistent in their attempts to reason about complex systems and learn to attend not only to structures, but also to processes and functions of complex systems.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.; Xu, J.

1999-04-06

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth; Xu, Jide

1999-01-01

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity.

Application of lag-k autocorrelation coefficient and the TGA signals approach to detecting and quantifying adulterations of extra virgin olive oil with inferior edible oils.

PubMed

Torrecilla, José S; García, Julián; García, Silvia; Rodríguez, Francisco

2011-03-04

The combination of lag-k autocorrelation coefficients (LCCs) and thermogravimetric analyzer (TGA) equipment is defined here as a tool to detect and quantify adulterations of extra virgin olive oil (EVOO) with refined olive (ROO), refined olive pomace (ROPO), sunflower (SO) or corn (CO) oils, when the adulterating agents concentration are less than 14%. The LCC is calculated from TGA scans of adulterated EVOO samples. Then, the standardized skewness of this coefficient has been applied to classify pure and adulterated samples of EVOO. In addition, this chaotic parameter has also been used to quantify the concentration of adulterant agents, by using successful linear correlation of LCCs and ROO, ROPO, SO or CO in 462 EVOO adulterated samples. In the case of detection, more than 82% of adulterated samples have been correctly classified. In the case of quantification of adulterant concentration, by an external validation process, the LCC/TGA approach estimates the adulterant agents concentration with a mean correlation coefficient (estimated versus real adulterant agent concentration) greater than 0.90 and a mean square error less than 4.9%. Copyright © 2011 Elsevier B.V. All rights reserved.

Anti-infective properties of the melanin-glucan complex obtained from medicinal tinder bracket mushroom, Fomes fomentarius (L.: Fr.) Fr. (Aphyllophoromycetideae).

PubMed

Seniuk, Olga F; Gorovoj, Leontiy F; Beketova, Galina V; Savichuk, Hatalia O; Rytik, Petr G; Kucherov, Igor I; Prilutskay, Alla B; Prilutsky, Alexandr I

2011-01-01

The goal of this investigation was to comparatively study the efficiency of traditionally used anti-infective drugs and biopolymer complexes originated from the medicinal mushroom Fomes fomentarius (L.:Fr.) Fr.: 1) water-soluble melanin-glucan complex (MGC; -80% melanins and -20% beta-glucans) and 2) insoluble chitin-glucan-melanin complex (ChGMC; -70% chitin, -20% beta-glucans, and -10% melanins). Infectious materials (Helicobacter pylori, Candida albicans, and Herpes vulgaris I and HIV-1(zmb) were used in pure cultures of in vitro and in vivo models on experimental animals. Comparison studies of fungal biopolymers and effective modern antifungal, antibacterial, and antiviral drugs were used in in vitro models. The comparative clinical efficiency of ChGMC and of etiotropic pharmaceuticals in models of H. pylori, C. albicans, and H. vulgaris I infection contamination were studied. Using in vitro models, it was established that MGC completely depresses growth of C. albicans. MGC had an antimicrobial effect on H. pylori identical to erythromycin in all concentrations, and had a stronger action on this bacterium than other tested antibiotics. Tested MGC possesses simultaneously weak toxicity and high anti-HIV-1 activity in comparison with zidovudine (Retrovir). The obtained results show that CLUDDT therapy in Wistar rats with the application of ChGMC is, on average, 1.35-1.43 times as effective as a traditional one. Considering the absence of MGC and ChGMC toxic properties on blood cells even in very high concentrations, these complexes may be used as a source of biopolymers for the creation of essentially new agents for wide application in infectious pathology.

Moringa isothiocyanate complexed with α-cyclodextrin: a new perspective in neuroblastoma treatment.

PubMed

Giacoppo, Sabrina; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

2017-07-14

Several lines of evidence suggest the consume of natural products for cancer prevention or treatment. In particular, isothiocyanates (ITCs) exerting anti-cancer properties, have received great interest as potential chemotherapeutic agents. This study was designed to assess the anti-proliferative activities of a new preparation of Moringa oleifera-derived 4-(α-L-rhamnopyranosyloxy)benzyl ITC (moringin) complexed with alpha-cyclodextrin (moringin + α-CD; MAC) on SH-SY5Y human neuroblastoma cells. This new formulation arises in the attempt to overcome the poor solubility and stability of moringin alone in aqueous media. SH-SY5Y cells were cultured and exposed to increasing concentrations of MAC (1.0, 2.5 and 5.0 μg). Cell proliferation was examined by MTT and cell count assays. The cytotoxic activity of the MAC complex was assessed by lactate dehydrogenase (LDH) assay and trypan blue exclusion test. In addition, western blotting analyses for the main apoptosis-related proteins were performed. Treatment of SH-SY5Y cells with the MAC complex reduced cell growth in concentration dependent manner. Specifically, MAC exhibited a potent action in inhibiting the PI3K/Akt/mTOR pathway, whose aberrant activation was found in many types of cancer. MAC was also found to induce the nuclear factor-κB (NF-κB) p65 activation by phosphorylation and its translocation into the nucleus. Moreover, treatment with MAC was able to down-regulate MAPK pathway (results focused on JNK and p38 expression). Finally, MAC was found to trigger apoptotic death pathway (based on expression levels of cleaved-caspase 3, Bax/Bcl-2 balance, p53 and p21). These findings suggest that use of MAC complex may open novel perspectives to improve the poor prognosis of patients with neuroblastoma.

Application of poly (ethyleneimine) solution as a binding agent in DGT technique for measurement of heavy metals in water.

PubMed

Sui, Dian-Peng; Fan, Hong-Tao; Li, Jing; Li, You; Li, Qiong; Sun, Ting

2013-09-30

A 0.050 mol L(-1) solution of poly (ethyleneimine) (PEI), had been used as a novel binding agent of diffusive gradients in thin-films (DGT) technique (PEI-DGT) for measuring the concentrations of labile Cu(2+), Cd(2+) and Pb(2+) in waters. The binding capacities of the PEI-DGT for Cu(2+), Cd(2+) and Pb(2+) were 11.8, 10.2 and 10.6 μmol L(-1), respectively. The performance of PEI-DGT was independence of pH in the range of 4-8 and ionic strength in the range from 1×10(-4) to 0.1 mol L(-1) (as NaNO3). PEI-DGT could measure 104.7±5.2% of the total concentration of Cd(2+) (0.500 mg L(-1)), 95.2±4.3% of the total Cu(2+) (0.500 mg L(-1)) and 99.2±3.4% of the total Pb(2+) (0.500 mg L(-1)) in synthetic solution. Effects of the ligands on the measurement of labile metals were also investigated in synthetic solutions containing the various concentrations of EDTA and humic acid. In EDTA solution, the concentrations of labile metals measured by PEI-DGT showed good agreement with the theoretical concentrations of free metal ions. In humic acid solution, the concentrations of labile metals measured by PEI-DGT decreased with the increase of the concentrations of humic acid. Several DGT devices with various binding agents, including PEI, sodium polyacrylate and poly(4-styrenesulfonate) solution, were used for the measurement of labile fractions of Cu(2+), Cd(2+) and Pb(2+) in the spiked waters and in mine wastewaters. The results showed that the concentrations of labile metal measured by DGT devices with different binding agents could be significantly different, indicating that the labile fractions of metals were dependent on the binding strength of the binding agents with metals. By choosing binding agents, the useful information on the speciation and bioavailability of the analytes can be provided. Copyright © 2013 Elsevier B.V. All rights reserved.

Antimalarial and antimicrobial activities of 8-Aminoquinoline-Uracils metal complexes

PubMed Central

Phopin, Kamonrat; Sinthupoom, Nujarin; Treeratanapiboon, Lertyot; Kunwittaya, Sarun; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong

2016-01-01

8-Aminoquinoline (8AQ) derivatives have been reported to have antimalarial, anticancer, and antioxidant activities. This study investigated the potency of 8AQ-5-substituted (iodo and nitro) uracils metal (Mn, Cu, Ni) complexes (1-6) as antimalarial and antimicrobial agents. Interestingly, all of these metal complexes (1-6) showed fair antimalarial activities. Moreover, Cu complexes 2 (8AQ-Cu-5Iu) and 5 (8AQ-Cu-5Nu) exerted antimicrobial activities against Gram-negative bacteria including P. shigelloides and S. dysenteriae. The results reveal application of 8AQ and its metal complexes as potential compounds to be further developed as novel antimalarial and antibacterial agents. PMID:27103894

Antimalarial and antimicrobial activities of 8-Aminoquinoline-Uracils metal complexes.

PubMed

Phopin, Kamonrat; Sinthupoom, Nujarin; Treeratanapiboon, Lertyot; Kunwittaya, Sarun; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong

2016-01-01

8-Aminoquinoline (8AQ) derivatives have been reported to have antimalarial, anticancer, and antioxidant activities. This study investigated the potency of 8AQ-5-substituted (iodo and nitro) uracils metal (Mn, Cu, Ni) complexes (1-6) as antimalarial and antimicrobial agents. Interestingly, all of these metal complexes (1-6) showed fair antimalarial activities. Moreover, Cu complexes 2 (8AQ-Cu-5Iu) and 5 (8AQ-Cu-5Nu) exerted antimicrobial activities against Gram-negative bacteria including P. shigelloides and S. dysenteriae. The results reveal application of 8AQ and its metal complexes as potential compounds to be further developed as novel antimalarial and antibacterial agents.

The hazardous hexavalent chromium formed on trivalent chromium conversion coating: The origin, influence factors and control measures.

PubMed

Li, Jinhua; Yao, Chenlan; Liu, Yanbiao; Li, Di; Zhou, Baoxue; Cai, Weimin

2012-06-30

In this paper, the effects of processing parameters and constituents of treating-agent on the presence of hazardous hexavalent chromium on trivalent chromium conversion coating were studied. Results showed that shorter immersion time, lower bath pH value as well as lower working and baking temperatures retarded the presence of hexavalent chromium. In addition, the concentration of hexavalent chromium on conversion coatings prepared by the oxalic acid treating-agent was far greater than those on conversion coatings prepared by formic acid and acetic acid treating-agents. Results also indicated that the concentration of hexavalent chromium on conversion coatings was enhanced due to the addition of bivalent cobalt and nitrate anion in treating-agent, especially for oxalic acid conversion coating. However, the addition of hydroxyl compound d-gluconic acid in treating-agent could reduce the concentration of hexavalent chromium effectively. Moreover, a possible formation mechanism of hexavalent chromium on trivalent conversion coating was proposed. Findings of this study provide a better understanding of the formation of hexavalent chromium on trivalent chromium conversion coating and can facilitate the management of trivalent chromium treating-agents and trivalent chromium fasteners. Copyright © 2012 Elsevier B.V. All rights reserved.

Design and characterization of an APC-specific serpin for the treatment of hemophilia

PubMed Central

Polderdijk, Stéphanie G. I.; Adams, Ty E.; Ivanciu, Lacramioara; Camire, Rodney M.; Baglin, Trevor P.

2017-01-01

Hemophilia is a bleeding disorder caused by deficiency in factors VIII or IX, the two components of the intrinsic Xase complex. Treatment with replacement factor can lead to the development of inhibitory antibodies, requiring the use of bypassing agents such as factor VIIa and factor concentrates. An alternative approach to bypass the Xase complex is to inhibit endogenous anticoagulant activities. Activated protein C (APC) breaks down the complex that produces thrombin by proteolytically inactivating factor Va. Defects in this mechanism (eg, factor V Leiden) are associated with thrombosis but result in less severe bleeding when co-inherited with hemophilia. Selective inhibition of APC might therefore be effective for the treatment of hemophilia. The endogenous inhibitors of APC are members of the serpin family: protein C inhibitor (PCI) and α1-antitrypsin (α1AT); however, both exhibit poor reactivity and selectivity for APC. We mutated residues in and around the scissile P1-P1′ bond in PCI and α1AT, resulting in serpins with the desired specificity profile. The lead candidate was shown to promote thrombin generation in vitro and to restore fibrin and platelet deposition in an intravital laser injury model in hemophilia B mice. The power of targeting APC was further demonstrated by the complete normalization of bleeding after a severe tail clip injury in these mice. These results demonstrate that the protein C anticoagulant system can be successfully targeted by engineered serpins and that administration of such agents is effective at restoring hemostasis in vivo. PMID:27789479

Selective and sensitive speciation analysis of Cr(VI) and Cr(III), at sub-μgL-1 levels in water samples by electrothermal atomic absorption spectrometry after electromembrane extraction.

PubMed

Tahmasebi, Zeinab; Davarani, Saied Saeed Hosseiny

2016-12-01

In this work, electromembrane extraction in combination with electrothermal atomic absorption spectrometry (ET-AAS) was investigated for speciation, preconcentration and quantification of Cr(VI) and Cr(III) in water samples through the selective complexation of Cr(VI) with 1,5-diphenylcarbazide (DPC) as a complexing agent. DPC reduces Cr(VI) to Cr(III) ions and then Cr(III) species are extracted based on electrokinetic migration of their cationic complex (Cr(III)-DPC) toward the negative electrode placed in the hollow fiber. Also, once oxidized to Cr(VI), Cr(III) ions in initial sample were determined by this procedure. The influence of extraction parameters such as pH, type of organic solvent, chelating agent concentration, stirring rate, extraction time and applied voltage were evaluated following a one-at-a-time optimization approach. Under optimized conditions, the extracted analyte was quantified by ETAAS, with an acceptable linearity in the range of 0.05-5ngmL -1 (R 2 value=0.996), and a repeatability (%RSD) between 3.7% and 12.2% (n=4) for 5.0 and 1.0ngmL -1 of Cr(VI), respectively. Also, we obtained an enrichment factor of 110 that corresponded to the recovery of 66%. The detection limit (S/N ratio of 3:1) was 0.02ngmL -1 . Finally, this new method was successfully employed to determine Cr(III) and Cr(VI) species in real water samples. Copyright © 2016. Published by Elsevier B.V.

Coencapsulation of oxygen carriers and glucose oxidase in polyelectrolyte complex capsules for the enhancement of D-gluconic acid and delta-gluconolactone production.

PubMed

Bucko, Marek; Gemeiner, Peter; Vikartovská, Alica; Mislovicová, Danica; Lacík, Igor; Tkác, Ján

2010-04-01

A novel encapsulated oxidative biocatalyst comprising glucose oxidase (GOD) coencapsulated with oxygen carriers within polyelectrolyte complex capsules was developed for the production of D-gluconic acid and delta-gluconolactone. The capsules containing immobilized GOD were produced by polyelectrolyte complexation with sodium alginate (SA) and cellulose sulfate (CS) as polyanions, poly(methylene-co-guanidine) (PMCG) as the polycation, CaCl(2) as the gelling agent and NaCl as the antigelling agent (GOD-SA-CS/PMCG capsules). Poly(dimethylsiloxane) (PDMS) and an emulsion of n-dodecane (DOD) or perfluorodecaline (PFD) with PDMS were used as the oxygen carriers and MnO(2) was used as a hydrogen peroxide decomposition catalyst. Water-soluble PDMS was found to act as both an oxygen carrier and an emulsifier of water-insoluble DOD and PFD. Stable microcapsules could be produced with concentrations of up to 4% (w/w) of PDMS, 10% (w/w) of DOD and PFD, and 25% (w/w) of MnO(2) in the polyanion solution of SA and CS. Roughly a two-fold increase in the GOD activity from 21.0+/-1.1 to 38.4+/-2.0 U*g(-1) and product space-time yields (STY) from 44.3+/-2.0 to 83.4+/-3.4 g*H*day(-1) could be achieved utilizing coencapsulated oxygen carriers compared to GOD encapsulated in the absence of oxygen carriers. This enhanced production does not significantly depend on the selected oxygen carrier under the conditions used in this study.

Metareasoning and Social Evaluations in Cognitive Agents

NASA Astrophysics Data System (ADS)

Pinyol, Isaac; Sabater-Mir, Jordi

Reputation mechanisms have been recognized one of the key technologies when designing multi-agent systems. They are specially relevant in complex open environments, becoming a non-centralized mechanism to control interactions among agents. Cognitive agents tackling such complex societies must use reputation information not only for selecting partners to interact with, but also in metareasoning processes to change reasoning rules. This is the focus of this paper. We argue about the necessity to allow, as a cognitive systems designers, certain degree of freedom in the reasoning rules of the agents. We also describes cognitive approaches of agency that support this idea. Furthermore, taking as a base the computational reputation model Repage, and its integration in a BDI architecture, we use the previous ideas to specify metarules and processes to modify at run-time the reasoning paths of the agent. In concrete we propose a metarule to update the link between Repage and the belief base, and a metarule and a process to update an axiom incorporated in the belief logic of the agent. Regarding this last issue we also provide empirical results that show the evolution of agents that use it.

Foundations of “new” social science: Institutional legitimacy from philosophy, complexity science, postmodernism, and agent-based modeling

PubMed Central

Henrickson, Leslie; McKelvey, Bill

2002-01-01

Since the death of positivism in the 1970s, philosophers have turned their attention to scientific realism, evolutionary epistemology, and the Semantic Conception of Theories. Building on these trends, Campbellian Realism allows social scientists to accept real-world phenomena as criterion variables against which theories may be tested without denying the reality of individual interpretation and social construction. The Semantic Conception reduces the importance of axioms, but reaffirms the role of models and experiments. Philosophers now see models as “autonomous agents” that exert independent influence on the development of a science, in addition to theory and data. The inappropriate molding effects of math models on social behavior modeling are noted. Complexity science offers a “new” normal science epistemology focusing on order creation by self-organizing heterogeneous agents and agent-based models. The more responsible core of postmodernism builds on the idea that agents operate in a constantly changing web of interconnections among other agents. The connectionist agent-based models of complexity science draw on the same conception of social ontology as do postmodernists. These recent developments combine to provide foundations for a “new” social science centered on formal modeling not requiring the mathematical assumptions of agent homogeneity and equilibrium conditions. They give this “new” social science legitimacy in scientific circles that current social science approaches lack. PMID:12011408

The Effect of Temperature and Concentration of Foaming Agent to the β-Carotene Content in Product Derived from Carrots

NASA Astrophysics Data System (ADS)

Fardiyah, Qonitah; Rumhayati, Barlah; Husnul Khotimah, Yuniesti

2018-01-01

Carrot (Daucus carota L) is vegetable that contain body essetial vitamins, especially β-carotene. In this research, the essense of fresh carrots are taken and processed to carrot powder using foam mat drying method. This research aims to study the effect of temperature and concentration of foaming agent to the β-carotene content in product derived from carrots. The temperature variation that used in this research are 40°C, 50°C, 60°C and 70°C, while he variation of foaming agent (tween 80) are 0,01% (v/v); 0,1%(v/v); 0,2%(v/v) and 0,3%(v/v). The results shows that the maximum drying temperature is 50°C with β-carotene content 10.55 mg/kg and the maximum concentration of foaming agent (tween 80) is 0.2% (v/v) with β-carotene content 10.36 mg/kg.

Excellent approach to modeling urban expansion by fuzzy cellular automata: agent base model

NASA Astrophysics Data System (ADS)

Khajavigodellou, Yousef; Alesheikh, Ali A.; Mohammed, Abdulrazak A. S.; Chapi, Kamran

2014-09-01

Recently, the interaction between humans and their environment is the one of important challenges in the world. Landuse/ cover change (LUCC) is a complex process that includes actors and factors at different social and spatial levels. The complexity and dynamics of urban systems make the applicable practice of urban modeling very difficult. With the increased computational power and the greater availability of spatial data, micro-simulation such as the agent based and cellular automata simulation methods, has been developed by geographers, planners, and scholars, and it has shown great potential for representing and simulating the complexity of the dynamic processes involved in urban growth and land use change. This paper presents Fuzzy Cellular Automata in Geospatial Information System and remote Sensing to simulated and predicted urban expansion pattern. These FCA-based dynamic spatial urban models provide an improved ability to forecast and assess future urban growth and to create planning scenarios, allowing us to explore the potential impacts of simulations that correspond to urban planning and management policies. A fuzzy inference guided cellular automata approach. Semantic or linguistic knowledge on Land use change is expressed as fuzzy rules, based on which fuzzy inference is applied to determine the urban development potential for each pixel. The model integrates an ABM (agent-based model) and FCA (Fuzzy Cellular Automata) to investigate a complex decision-making process and future urban dynamic processes. Based on this model rapid development and green land protection under the influences of the behaviors and decision modes of regional authority agents, real estate developer agents, resident agents and non- resident agents and their interactions have been applied to predict the future development patterns of the Erbil metropolitan region.

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

PubMed Central

Estelrich, Joan; Sánchez-Martín, María Jesús; Busquets, Maria Antònia

2015-01-01

Magnetic resonance imaging (MRI) has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times (T1, spin–lattice relaxation and T2, spin–spin relaxation) of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents) are administered prior to the scanning. Shortening T1 and T2 increases the corresponding relaxation rates, 1/T1 and 1/T2, producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T2-weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions), providing positive contrast in T1-weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor) targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively. Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents. PMID:25834422

Crystal structures of human group-VIIA phospholipase A2 inhibited by organophosphorus nerve agents exhibit non-aged complexes

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

Samanta, Uttamkumar; Kirby, Stephen D.; Srinivasan, Prabhavathi

The enzyme group-VIIA phospholipase A2 (gVIIA-PLA2) is bound to lipoproteins in human blood and hydrolyzes the ester bond at the sn-2 position of phospholipid substrates with a short sn-2 chain. The enzyme belongs to a serine hydrolase superfamily of enzymes, which react with organophosphorus (OP) nerve agents. OPs ultimately exert their toxicity by inhibiting human acetycholinesterase at nerve synapses, but may additionally have detrimental effects through inhibition of other serine hydrolases. We have solved the crystal structures of gVIIA-PLA2 following inhibition with the OPs diisopropylfluorophosphate, sarin, soman and tabun. The sarin and soman complexes displayed a racemic mix of P{submore » R} and P{sub S} stereoisomers at the P-chiral center. The tabun complex displayed only the P{sub R} stereoisomer in the crystal. In all cases, the crystal structures contained intact OP adducts that had not aged. Aging refers to a secondary process OP complexes can go through, which dealkylates the nerve agent adduct and results in a form that is highly resistant to either spontaneous or oxime-mediated reactivation. Non-aged OP complexes of the enzyme were corroborated by trypsin digest and matrix-assisted laser desorption ionization mass spectrometry of OP-enzyme complexes. The lack of stereoselectivity of sarin reaction was confirmed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate the unbound stereoisomers of sarin following incubation with enzyme. The structural details and characterization of nascent reactivity of several toxic nerve agents is discussed with a long-term goal of developing gVIIA-PLA2 as a catalytic bioscavenger of OP nerve agents.« less

Crystal structures of human group-VIIA phospholipase A2 inhibited by organophosphorus nerve agents exhibit non-aged complexes.

PubMed

Samanta, Uttamkumar; Kirby, Stephen D; Srinivasan, Prabhavathi; Cerasoli, Douglas M; Bahnson, Brian J

2009-08-15

The enzyme group-VIIA phospholipase A2 (gVIIA-PLA2) is bound to lipoproteins in human blood and hydrolyzes the ester bond at the sn-2 position of phospholipid substrates with a short sn-2 chain. The enzyme belongs to a serine hydrolase superfamily of enzymes, which react with organophosphorus (OP) nerve agents. OPs ultimately exert their toxicity by inhibiting human acetycholinesterase at nerve synapses, but may additionally have detrimental effects through inhibition of other serine hydrolases. We have solved the crystal structures of gVIIA-PLA2 following inhibition with the OPs diisopropylfluorophosphate, sarin, soman and tabun. The sarin and soman complexes displayed a racemic mix of P(R) and P(S) stereoisomers at the P-chiral center. The tabun complex displayed only the P(R) stereoisomer in the crystal. In all cases, the crystal structures contained intact OP adducts that had not aged. Aging refers to a secondary process OP complexes can go through, which dealkylates the nerve agent adduct and results in a form that is highly resistant to either spontaneous or oxime-mediated reactivation. Non-aged OP complexes of the enzyme were corroborated by trypsin digest and matrix-assisted laser desorption ionization mass spectrometry of OP-enzyme complexes. The lack of stereoselectivity of sarin reaction was confirmed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate the unbound stereoisomers of sarin following incubation with enzyme. The structural details and characterization of nascent reactivity of several toxic nerve agents is discussed with a long-term goal of developing gVIIA-PLA2 as a catalytic bioscavenger of OP nerve agents.

Formulation and method for preparing gels comprising hydrous aluminum oxide

DOEpatents

Collins, Jack L.

2014-06-17

Formulations useful for preparing hydrous aluminum oxide gels contain a metal salt including aluminum, an organic base, and a complexing agent. Methods for preparing gels containing hydrous aluminum oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including aluminum, an organic base, and a complexing agent.

Isonitrile radionuclide complexes for labelling and imaging agents

DOEpatents

Jones, Alun G.; Davison, Alan; Abrams, Michael J.

1984-06-04

A coordination complex of an isonitrile ligand and radionuclide such as Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb and Ta, is useful as a diagnostic agent for labelling liposomes or vesicles, and selected living cells containing lipid membranes, such as blood clots, myocardial tissue, gall bladder tissue, etc.

Formulation and method for preparing gels comprising hydrous cerium oxide

DOEpatents

Collins, Jack L; Chi, Anthony

2013-05-07

Formulations useful for preparing hydrous cerium oxide gels contain a metal salt including cerium, an organic base, and a complexing agent. Methods for preparing gels containing hydrous cerium oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including cerium, an organic base, and a complexing agent.

Reducing the Complexity of an Agent-Based Local Heroin Market Model

PubMed Central

Heard, Daniel; Bobashev, Georgiy V.; Morris, Robert J.

2014-01-01

This project explores techniques for reducing the complexity of an agent-based model (ABM). The analysis involved a model developed from the ethnographic research of Dr. Lee Hoffer in the Larimer area heroin market, which involved drug users, drug sellers, homeless individuals and police. The authors used statistical techniques to create a reduced version of the original model which maintained simulation fidelity while reducing computational complexity. This involved identifying key summary quantities of individual customer behavior as well as overall market activity and replacing some agents with probability distributions and regressions. The model was then extended to allow external market interventions in the form of police busts. Extensions of this research perspective, as well as its strengths and limitations, are discussed. PMID:25025132

Hypercompetitive Environments: An Agent-based model approach

NASA Astrophysics Data System (ADS)

Dias, Manuel; Araújo, Tanya

Information technology (IT) environments are characterized by complex changes and rapid evolution. Globalization and the spread of technological innovation have increased the need for new strategic information resources, both from individual firms and management environments. Improvements in multidisciplinary methods and, particularly, the availability of powerful computational tools, are giving researchers an increasing opportunity to investigate management environments in their true complex nature. The adoption of a complex systems approach allows for modeling business strategies from a bottom-up perspective — understood as resulting from repeated and local interaction of economic agents — without disregarding the consequences of the business strategies themselves to individual behavior of enterprises, emergence of interaction patterns between firms and management environments. Agent-based models are at the leading approach of this attempt.

Heteroleptic Copper(I) Complexes of "Scorpionate" Bis-pyrazolyl Carboxylate Ligand with Auxiliary Phosphine as Potential Anticancer Agents: An Insight into Cytotoxic Mode.

PubMed

Khan, Rais Ahmad; Usman, Mohammad; Dhivya, Rajakumar; Balaji, Perumalsamy; Alsalme, Ali; AlLohedan, Hamad; Arjmand, Farukh; AlFarhan, Khalid; Akbarsha, Mohammad Abdulkader; Marchetti, Fabio; Pettinari, Claudio; Tabassum, Sartaj

2017-03-24

New copper(I) complexes [CuCl(PPh 3 )(L)] (1: L = L A  = 4-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane; (2: L = L B  = 3-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane) were prepared and characterised by elemental analysis and various spectroscopic techniques such as FT-IR, NMR, UV-Vis, and ESI-MS. The molecular structures of complexes 1 and 2 were analyzed by theoretical B3LYP/DFT method. Furthermore, in vitro DNA binding studies were carried out to check the ability of complexes 1 and 2 to interact with native calf thymus DNA (CT-DNA) using absorption titration, fluorescence quenching and circular dichroism, which is indicative of more avid binding of the complex 1. Moreover, DNA mobility assay was also conducted to study the concentration-dependent cleavage pattern of pBR322 DNA by complex 1, and the role of ROS species to have a mechanistic insight on the cleavage pattern, which ascertained substantial roles by both hydrolytic and oxidative pathways. Additionally, we analyzed the potential of the interaction of complex 1 with DNA and enzyme (Topo I and II) with the aid of molecular modeling. Furthermore, cytotoxic activity of complex 1 was tested against HepG2 cancer cell lines. Thus, the potential of the complex 1 is promising though further in vivo investigations may be required before subjecting it to clinical trials.

A Computational Model Predicting Disruption of Blood Vessel Development

PubMed Central

Kleinstreuer, Nicole; Dix, David; Rountree, Michael; Baker, Nancy; Sipes, Nisha; Reif, David; Spencer, Richard; Knudsen, Thomas

2013-01-01

Vascular development is a complex process regulated by dynamic biological networks that vary in topology and state across different tissues and developmental stages. Signals regulating de novo blood vessel formation (vasculogenesis) and remodeling (angiogenesis) come from a variety of biological pathways linked to endothelial cell (EC) behavior, extracellular matrix (ECM) remodeling and the local generation of chemokines and growth factors. Simulating these interactions at a systems level requires sufficient biological detail about the relevant molecular pathways and associated cellular behaviors, and tractable computational models that offset mathematical and biological complexity. Here, we describe a novel multicellular agent-based model of vasculogenesis using the CompuCell3D (http://www.compucell3d.org/) modeling environment supplemented with semi-automatic knowledgebase creation. The model incorporates vascular endothelial growth factor signals, pro- and anti-angiogenic inflammatory chemokine signals, and the plasminogen activating system of enzymes and proteases linked to ECM interactions, to simulate nascent EC organization, growth and remodeling. The model was shown to recapitulate stereotypical capillary plexus formation and structural emergence of non-coded cellular behaviors, such as a heterologous bridging phenomenon linking endothelial tip cells together during formation of polygonal endothelial cords. Molecular targets in the computational model were mapped to signatures of vascular disruption derived from in vitro chemical profiling using the EPA's ToxCast high-throughput screening (HTS) dataset. Simulating the HTS data with the cell-agent based model of vascular development predicted adverse effects of a reference anti-angiogenic thalidomide analog, 5HPP-33, on in vitro angiogenesis with respect to both concentration-response and morphological consequences. These findings support the utility of cell agent-based models for simulating a morphogenetic series of events and for the first time demonstrate the applicability of these models for predictive toxicology. PMID:23592958

Fluorescence and electron paramagnetic resonance studies of norfloxacin and N-donor mixed-ligand ternary copper(II) complexes: Stability and interaction with SDS micelles

NASA Astrophysics Data System (ADS)

Vignoli Muniz, Gabriel S.; Incio, Jimmy Llontop; Alves, Odivaldo C.; Krambrock, Klaus; Teixeira, Letícia R.; Louro, Sonia R. W.

2018-01-01

The stability of ternary copper(II) complexes of a heterocyclic ligand, L (L being 2,2‧-bipyridine (bipy) or 1,10-phenanthroline (phen)) and the fluorescent antibacterial agent norfloxacin (NFX) as the second ligand was studied at pH 7.4 and different ionic strengths. Fluorescence quenching upon titration of NFX with the binary complexes allowed to obtain stability constants for NFX binding, Kb, as a function of ionic strength. The Kb values vary by more than two orders of magnitude when buffer concentration varies from 0.5 to 100 mM. It was observed that previously synthesized ternary complexes dissociate in buffer according with the obtained stability constants. This shows that equimolar solutions of NFX and binary complexes are equivalent to solutions of synthesized ternary complexes. The interaction of the ternary copper complexes with anionic SDS (sodium dodecyl sulfate) micelles was studied by fluorescence and electron paramagnetic resonance (EPR). Titration of NFX-loaded SDS micelles with the complexes Cu:L allowed to determine the stability constants inside the micelles. Fluorescence quenching demonstrated that SDS micelles increase the stability constants by factors around 50. EPR spectra gave details of the copper(II) local environment, and demonstrated that the structure of the ternary complexes inside SDS micelles is different from that in buffer. Mononuclear ternary complexes formed inside the micelles, while in buffer most ternary complexes are binuclear. The results show that anionic membrane interfaces increase formation of copper fluoroquinolone complexes, which can influence bioavailability, membrane diffusion, and mechanism of action of the antibiotics.

Biomedical Nanocrystal Agents: Design, Synthesis, and Applications

NASA Astrophysics Data System (ADS)

Cho, Minjung

In these days, nanomaterials are applied in a variety of biomedical applications including magnetic resonance imaging (MRI), cell imaging, drug delivery, and cell separation. Most MRI contrast agents affect the longitudinal relaxation time (T1) and transverse relaxation time (T2 ) of water protons in the tissue and result in increased positive or negative contrast. Here, we report the optimization of r1 (1/T 1) or r2 (1/T2) relaxivity dynamics with diameter controlled gadolinium oxide nanocrystals (2˜22 nm) and iron based magnetic nanocrystals (4 ˜33 nm). The r1 and r2 MR relaxivity values of hydrated nanocrystals were optimized and examined depending on their core diameter, surface coating, and compositions; the high r1 value of gadolinium oxide was 40-60 S-1mM-1, which is 10-15 fold higher than that of commercial Gd (III) chelates (4.3˜4.6 S-1mM-1). Moreover, in vitro toxicological studies revealed that polymer coated nanocrystals suspensions had no significant effect on human dermal fibroblast (HDF) cells even at high concentration. Towards multimodal imaging or multifunctional ability, we developed the iron oxide/QDs complexes, which consist of cores of iron oxide that act as nucleation sites for fluorescent QDs. The choice of variable QDs helped to visualize and remove large iron oxide materials in a magnetic separation. Additionally, diluted materials concentrated on the magnet could be fluorescently detected even at very low concentration. The designed MRI or multifunctional nanomaterials will give great and powerful uses in biomedical applications.

Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action

PubMed Central

Roy, Ranita; Tiwari, Monalisa; Donelli, Gianfranco; Tiwari, Vishvanath

2018-01-01

ABSTRACT Biofilm refers to the complex, sessile communities of microbes found either attached to a surface or buried firmly in an extracellular matrix as aggregates. The biofilm matrix surrounding bacteria makes them tolerant to harsh conditions and resistant to antibacterial treatments. Moreover, the biofilms are responsible for causing a broad range of chronic diseases and due to the emergence of antibiotic resistance in bacteria it has really become difficult to treat them with efficacy. Furthermore, the antibiotics available till date are ineffective for treating these biofilm related infections due to their higher values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), which may result in in-vivo toxicity. Hence, it is critically important to design or screen anti-biofilm molecules that can effectively minimize and eradicate biofilm related infections. In the present article, we have highlighted the mechanism of biofilm formation with reference to different models and various methods used for biofilm detection. A major focus has been put on various anti-biofilm molecules discovered or tested till date which may include herbal active compounds, chelating agents, peptide antibiotics, lantibiotics and synthetic chemical compounds along with their structures, mechanism of action and their respective MICs, MBCs, minimum biofilm inhibitory concentrations (MBICs) as well as the half maximal inhibitory concentration (IC50) values available in the literature so far. Different mode of action of anti biofilm molecules addressed here are inhibition via interference in the quorum sensing pathways, adhesion mechanism, disruption of extracellular DNA, protein, lipopolysaccharides, exopolysaccharides and secondary messengers involved in various signaling pathways. From this study, we conclude that the molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby investigating its effective delivery in the host. It should also be ensured that minimum effective concentration of these molecules must be capable of eradicating biofilm infections with maximum potency without posing any adverse side effects on the host. PMID:28362216

Benzotriazoles, alkylphenols and bisphenol A in municipal wastewaters and in the Glatt River, Switzerland.

PubMed

Voutsa, Dimitra; Hartmann, Paul; Schaffner, Christian; Giger, Walter

2006-09-01

Many organic micropollutants occur at trace concentrations in municipal wastewater effluents and in the aquatic environment. Some of these xenobiotic chemicals can be considered as 'emerging' contaminants and some are suspect to have endocrine disrupting effects. Among the latter are nonylphenol (NP), octylphenol (OP) and bisphenol A (BPA), which deserve special attention due to their ubiquitous occurrence in the aquatic environment. The complexing agents benzotriazole (BT) and tolyltriazole (TT) are applied as anticorrosive agents (e.g. in cooling and hydraulic fluids, in antifreezing fluids, in aircraft deicing fluids, in dish washing liquids for silver protection), as antifogging agents and as intermediates for the synthesis of various chemicals. The environmental occurrence of NP and OP is caused by the fact that they are intermediate products (metabolites) in the biodegradation of alkylphenol polyethoxylate surfactants. BPA is globally used for the production of polycarbonate and epoxy resins. BT, TT, NP, OP and BPA were quantitatively determined in municipal wastewater effluents in Switzerland and in the Glatt River. The analytes were enriched by solid-phase enrichment. BT and TT were determined underivatized by electrospray LC/tandem MS. Reversed-phase LC was performed on octylsilica columns with isocratic water/methanol elution. Multiple reaction monitoring of the positive ions provided selective and sensitive detection for reliable quantifications. NP, OP and BPA were determined by GC/MS after derivatization with N-methyl-N-(trimethylsilyl)-trifluoroacetamide. BT and TT concentrations in primary and secondary effluents of municipal wastewater treatment plants varied from below 10 to 100 microg/L. The ranges of the concentrations in the Glatt River in ng/L were 636-3,690 for BT, 122-628 for TT, 68-326 for NP, 6-22 for OP and 9-76 for BPA. The corresponding mass flows in g/d were 93-1,870 for BT, 18-360 for TT, 24-183 for NP, 1-16 for OP and 2-72 for BPA. The concentrations and mass flows of NP in the River Glatt were drastically lower than the analogous values found 15 years ago. Thus, a substantially decreased environmental exposure can be observed due to the reduction of the use of alkyphenol polyethoxylate surfactants in Switzerland. The current concentrations of NP, OP and BPA are within the ranges reported for weakly impacted surface waters. The investigated contaminants occur at quantitatively measurable but varying concentrations in municipal wastewaters and in the Glatt River reflecting their ubiquitous input into wastewaters and their different behaviour during biological wastewater treatment.

Removal of pharmaceuticals from MWTP effluent by nanofiltration and solar photo-Fenton using two different iron complexes at neutral pH.

PubMed

Miralles-Cuevas, S; Oller, I; Pérez, J A Sánchez; Malato, S

2014-11-01

In recent years, membrane technologies (nanofiltration (NF)/reverse osmosis (RO)) have received much attention for micropollutant separation from Municipal Wastewater Treatment Plant (MWTP) effluents. Practically all micropollutants are retained in the concentrate stream, which must be treated. Advanced Oxidation Processes (AOPs) have been demonstrated to be a good option for the removal of microcontaminants from water systems. However, these processes are expensive, and therefore, are usually combined with other techniques (such as membrane systems) in an attempt at cost reduction. One of the main costs in solar photo-Fenton comes from reagent consumption, mainly hydrogen peroxide and chemicals for pH adjustment. Thus, in this study, solar photo-Fenton was used to treat a real MWTP effluent with low initial iron (less than 0.2 mM) and hydrogen peroxide (less than 2 mM) concentrations. In order to work at neutral pH, iron complexing agents (EDDS and citrate) were used in the two cases studied: direct treatment of the MWTP effluent and treatment of the concentrate stream generated by NF. The degradation of five pharmaceuticals (carbamazepine, flumequine, ibuprofen, ofloxacin and sulfamethoxazole) spiked in the effluent at low initial concentrations (μg L(-1)) was monitored as the main variable in the pilot-plant-scale photo-Fenton experiments. In both effluents, pharmaceuticals were efficiently removed (>90%), requiring low accumulated solar energy (2 kJUV L(-1), key parameter in scaling up the CPC photoreactor) and low iron and hydrogen peroxide concentrations (reagent costs, 0.1 and 1.5 mM, respectively). NF provided a clean effluent, and the concentrate was positively treated by solar photo-Fenton with no significant differences between the direct MWTP effluent and NF concentrate treatments. Copyright © 2014 Elsevier Ltd. All rights reserved.

C-terminal Agrin Fragment as a potential marker for sarcopenia caused by degeneration of the neuromuscular junction.

PubMed

Drey, M; Sieber, C C; Bauer, J M; Uter, W; Dahinden, P; Fariello, R G; Vrijbloed, J W

2013-01-01

Sarcopenia is considered to be an enormous burden for both the individuals affected and for society at large. A multifactorial aetiology of this geriatric syndrome has been discussed. Amongst other pathomechanisms, the degeneration of the neuromuscular junction (NMJ) may be of major relevance. The intact balance between the pro-synaptic agent agrin and the anti-synaptic agent neurotrypsin ensures a structurally and functionally intact NMJ. Excessive cleavage of the native motoneuron-derived agrin by neurotrypsin into a C-terminal Agrin Fragment (CAF) leads to functional disintegration at the NMJ and may consecutively cause sarcopenia. The present study evaluates the hypothesis that CAF serum concentration is a potential marker for the loss of appendicular lean mass in older adults. It also explores how CAF concentration is influenced by vitamin D supplementation and physical exercise. Serum was taken from 69 (47 female) prefrail community-dwelling older adults participating in a training intervention study to measure the CAF concentration using the Western blot technique. All participants were supplemented orally with vitamin D3 before the training intervention period commenced. Appendicular lean mass (aLM) was evaluated by dual energy X-ray absorptiometry. Multiple linear regression models were used to identify factors significantly associated with CAF concentration. Appendicular lean mass, age and sex were identified as significant explanatory factors for CAF concentration. Gait speed and hand grip strength were not associated with CAF concentration. Male participants showed a strong correlation (r=-0.524) between CAF serum concentration and aLM, whereas this was not the case (r=-0.219) in females. Vitamin D supplementation and physical exercise were significantly associated with a reduction in CAF concentration, especially in participants with initially high CAF concentrations. C-terminal Agrin Fragment could be a potential marker for identifying sarcopenia in a subgroup of affected individuals in the future. The decline of muscle mass seems to be a CAF-associated process in males, whereas the situation in females may be more complex and multifactorial. CAF concentration is reduced by vitamin D supplementation and physical exercise and therefore suggests a potentially positive effect on NMJs. Further prospective studies of sarcopenic patients in addition to muscle biopsy and electromyographical investigations are planned to verify the external validity of the CAF concept. Copyright © 2012 Elsevier Inc. All rights reserved.

99mTc: Labeling Chemistry and Labeled Compounds

NASA Astrophysics Data System (ADS)

Alberto, R.; Abram, U.

This chapter reviews the radiopharmaceutical chemistry of technetium related to the synthesis of perfusion agents and to the labeling of receptor-binding biomolecules. To understand the limitations of technetium chemistry imposed by future application of the complexes in nuclear medicine, an introductory section analyzes the compulsory requirements to be considered when facing the incentive of introducing a novel radiopharmaceutical into the market. Requirements from chemistry, routine application, and market are discussed. In a subsequent section, commercially available 99mTc-based radiopharmaceuticals are treated. It covers the complexes in use for imaging the most important target organs such as heart, brain, or kidney. The commercially available radiopharmaceuticals fulfill the requirements outlined earlier and are discussed with this background. In a following section, the properties and perspectives of the different generations of radiopharmaceuticals are described in a general way, covering characteristics for perfusion agents and for receptor-specific molecules. Technetium chemistry for the synthesis of perfusion agents and the different labeling approaches for target-specific biomolecules are summarized. The review comprises a general introduction to the common approaches currently in use, employing the N x S4-x , [3+1] and 2-hydrazino-nicotinicacid (HYNIC) method as well as more recent strategies such as the carbonyl and the TcN approach. Direct labeling without the need of a bifunctional chelator is briefly reviewed as well. More particularly, recent developments in the labeling of concrete targeting molecules, the second generation of radiopharmaceuticals, is then discussed and prominent examples with antibodies/peptides, neuroreceptor targeting small molecules, myocardial imaging agents, vitamins, thymidine, and complexes relevant to multidrug resistance are given. In addition, a new approach toward peptide drug development is described. The section has a focus on coordination and labeling chemistry, but biological results are briefly summarized as well. The last (and shortest) section finally intends to give a (subjective) outlook for the future role of 99mTc-based radiopharmaceuticals. Critical comments are spread over the whole article but are concentrated in this section. Despite the increasing competition of diagnostic radiopharmacy by other commonly applied methods in medicine such as magnetic resonance imaging (MRI) or ultrasound, the authors are convinced that 99mTc will play a key role also in future if novel approaches are added and the requirements from chemistry biology and the market considered in research to a stronger extent.

Design and Simulation of Material-Integrated Distributed Sensor Processing with a Code-Based Agent Platform and Mobile Multi-Agent Systems

PubMed Central

Bosse, Stefan

2015-01-01

Multi-agent systems (MAS) can be used for decentralized and self-organizing data processing in a distributed system, like a resource-constrained sensor network, enabling distributed information extraction, for example, based on pattern recognition and self-organization, by decomposing complex tasks in simpler cooperative agents. Reliable MAS-based data processing approaches can aid the material-integration of structural-monitoring applications, with agent processing platforms scaled to the microchip level. The agent behavior, based on a dynamic activity-transition graph (ATG) model, is implemented with program code storing the control and the data state of an agent, which is novel. The program code can be modified by the agent itself using code morphing techniques and is capable of migrating in the network between nodes. The program code is a self-contained unit (a container) and embeds the agent data, the initialization instructions and the ATG behavior implementation. The microchip agent processing platform used for the execution of the agent code is a standalone multi-core stack machine with a zero-operand instruction format, leading to a small-sized agent program code, low system complexity and high system performance. The agent processing is token-queue-based, similar to Petri-nets. The agent platform can be implemented in software, too, offering compatibility at the operational and code level, supporting agent processing in strong heterogeneous networks. In this work, the agent platform embedded in a large-scale distributed sensor network is simulated at the architectural level by using agent-based simulation techniques. PMID:25690550

Design and simulation of material-integrated distributed sensor processing with a code-based agent platform and mobile multi-agent systems.

PubMed

Bosse, Stefan

2015-02-16

Multi-agent systems (MAS) can be used for decentralized and self-organizing data processing in a distributed system, like a resource-constrained sensor network, enabling distributed information extraction, for example, based on pattern recognition and self-organization, by decomposing complex tasks in simpler cooperative agents. Reliable MAS-based data processing approaches can aid the material-integration of structural-monitoring applications, with agent processing platforms scaled to the microchip level. The agent behavior, based on a dynamic activity-transition graph (ATG) model, is implemented with program code storing the control and the data state of an agent, which is novel. The program code can be modified by the agent itself using code morphing techniques and is capable of migrating in the network between nodes. The program code is a self-contained unit (a container) and embeds the agent data, the initialization instructions and the ATG behavior implementation. The microchip agent processing platform used for the execution of the agent code is a standalone multi-core stack machine with a zero-operand instruction format, leading to a small-sized agent program code, low system complexity and high system performance. The agent processing is token-queue-based, similar to Petri-nets. The agent platform can be implemented in software, too, offering compatibility at the operational and code level, supporting agent processing in strong heterogeneous networks. In this work, the agent platform embedded in a large-scale distributed sensor network is simulated at the architectural level by using agent-based simulation techniques.

Distributed containment control of heterogeneous fractional-order multi-agent systems with communication delays

NASA Astrophysics Data System (ADS)

Yang, Hongyong; Han, Fujun; Zhao, Mei; Zhang, Shuning; Yue, Jun

2017-08-01

Because many networked systems can only be characterized with fractional-order dynamics in complex environments, fractional-order calculus has been studied deeply recently. When diverse individual features are shown in different agents of networked systems, heterogeneous fractional-order dynamics will be used to describe the complex systems. Based on the distinguishing properties of agents, heterogeneous fractional-order multi-agent systems (FOMAS) are presented. With the supposition of multiple leader agents in FOMAS, distributed containment control of FOMAS is studied in directed weighted topologies. By applying Laplace transformation and frequency domain theory of the fractional-order operator, an upper bound of delays is obtained to ensure containment consensus of delayed heterogenous FOMAS. Consensus results of delayed FOMAS in this paper can be extended to systems with integer-order models. Finally, numerical examples are used to verify our results.

Neural correlates of consciousness during general anesthesia using functional magnetic resonance imaging (fMRI).

PubMed

Bonhomme, V; Boveroux, P; Brichant, J F; Laureys, S; Boly, M

2012-01-01

This paper reviews the current knowledge about the mechanisms of anesthesia-induced alteration of consciousness. It is now evident that hypnotic anesthetic agents have specific brain targets whose function is hierarchically altered in a dose-dependent manner. Higher order networks, thought to be involved in mental content generation, as well as sub-cortical networks involved in thalamic activity regulation seems to be affected first by increasing concentrations of hypnotic agents that enhance inhibitory neurotransmission. Lower order sensory networks are preserved, including thalamo-cortical connectivity into those networks, even at concentrations that suppress responsiveness, but cross-modal sensory interactions are inhibited. Thalamo-cortical connectivity into the consciousness networks decreases with increasing concentrations of those agents, and is transformed into an anti-correlated activity between the thalamus and the cortex for the deepest levels of sedation, when the subject is non responsive. Future will tell us whether these brain function alterations are also observed with hypnotic agents that mainly inhibit excitatory neurotransmission. The link between the observations made using fMRI and the identified biochemical targets of hypnotic anesthetic agents still remains to be identified.

The benefits of paired-agent imaging in molecular-guided surgery: an update on methods and applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tichauer, Kenneth M.

2016-03-01

One of the major complications with conventional imaging-agent-based molecular imaging, particularly for cancer imaging, is variability in agent delivery and nonspecific retention in biological tissue. Such factors can account to "swamp" the signal arising from specifically bound imaging agent, which is presumably indicative of the concentration of targeted biomolecule. In the 1950s, Pressman et al. proposed a method of accounting for these delivery and retention effects by normalizing targeted antibody retention to the retention of a co-administered "untargeted"/control imaging agent [1]. Our group resurrected the approach within the last 5 years, finding ways to utilize this so-called "paired-agent" imaging approach to directly quantify biomolecule concentration in tissue (in vitro, ex vivo, and in vivo) [2]. These novel paired-agent imaging approaches capable of quantifying biomolecule concentration provide enormous potential for being adapted to and optimizing molecular-guided surgery, which has a principle goal of identifying distinct biological tissues (tumor, nerves, etc…) based on their distinct molecular environment. This presentation will cover the principles and nuances of paired-agent imaging, as well as the current status of the field and future applications. [1] D. Pressman, E. D. Day, and M. Blau, "The use of paired labeling in the determination of tumor-localizing antibodies," Cancer Res, 17(9), 845-50 (1957). [2] K. M. Tichauer, Y. Wang, B. W. Pogue et al., "Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging," Phys Med Biol, 60(14), R239-69 (2015).

Biguanides inhibit complex I, II and IV of rat liver mitochondria and modify their functional properties.

PubMed

Drahota, Z; Palenickova, E; Endlicher, R; Milerova, M; Brejchova, J; Vosahlikova, M; Svoboda, P; Kazdova, L; Kalous, M; Cervinkova, Z; Cahova, M

2014-01-01

In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeability transition pore function. We used phenformin, which is more efficient than metformin, and evaluated its effect on rat liver mitochondria and isolated hepatocytes. In contrast to previously published data, we found that phenformin, after a 5 min pre-incubation, dose-dependently inhibits not only mitochondrial complex I but also complex II and IV activity in isolated mitochondria. The enzymes complexes inhibition is paralleled by the decreased respiratory control index and mitochondrial membrane potential. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca(2+) ions. Our data might be in agreement with the hypothesis of Schäfer (1976) that binding of biguanides to membrane phospholipids alters membrane properties in a non-specific manner and, subsequently, different enzyme activities are modified via lipid phase. However, our measurements of anisotropy of fluorescence of hydrophobic membrane probe diphenylhexatriene have not shown a measurable effect of membrane fluidity with the 1 mM concentration of phenformin that strongly inhibited complex I activity. Our data therefore suggest that biguanides could be considered as agents with high efficacy but low specifity.

Resistance of bacterial biofilms formed on stainless steel surface to disinfecting agent.

PubMed

Królasik, Joanna; Zakowska, Zofia; Krepska, Milena; Klimek, Leszek

2010-01-01

The natural ability of microorganisms for adhesion and biofilm formation on various surfaces is one of the factors causing the inefficiency of a disinfection agent, despite its proven activity in vitro. The aim of the study was to determine the effectiveness of disinfecting substances on bacterial biofilms formed on stainless steel surface. A universally applied disinfecting agent was used in the tests. Bacterial strains: Listeria innocua, Pseudomonas putida, Micrococcus luteus, Staphylococcus hominis strains, were isolated from food contact surfaces, after a cleaning and disinfection process. The disinfecting agent was a commercially available acid specimen based on hydrogen peroxide and peroxyacetic acid, the substance that was designed for food industry usage. Model tests were carried out on biofilm formed on stainless steel (type 304, no 4 finish). Biofilms were recorded by electron scanning microscope. The disinfecting agent in usable concentration, 0.5% and during 10 minutes was ineffective for biofilms. The reduction of cells in biofilms was only 1-2 logarithmic cycles. The use of the agent in higher concentration--1% for 30 minutes caused reduction of cell number by around 5 logarithmic cycles only in the case of one microorganism, M. luteus. For other types: L. innocua, P. putida, S. hominis, the requirements placed on disinfecting agents were not fulfilled. The results of experiments proved that bacterial biofilms are resistant to the disinfectant applied in its operational parameters. Disinfecting effectiveness was achieved after twofold increase of the agent's concentration.

Effects of carbon concentration and carbon to nitrogen ratio on the growth and sporulation of several biocontrol fungi.

PubMed

Gao, Li; Sun, Man H; Liu, Xing Z; Che, Yong S

2007-01-01

Effects of carbon concentration and carbon to nitrogen (C:N) ratio on six biocontrol fungal strains are reported in this paper. All fungal strains had extensive growth on the media supplemented with 6-12 gl(-1) carbon and C:N ratios from 10:1 to 80:1, and differed in nutrient requirements for sporulation. Except for the two strains of Paecilomyces lilacinus, all selected fungi attained the highest spore yields at a C:N ratio of 160:1 when the carbon concentration was 12 gl(-1) for Metarhizium anisopliae SQZ-1-21, 6 gl(-1) for M. anisopliae RS-4-1 and Trichoderma viride TV-1, and 8 gl(-1) for Lecanicillium lecanii CA-1-G. The optimal conditions for P. lilacinus sporulation were 8 gl(-1) carbon with a C:N ratio of 10:1 for M-14 and 12 gl(-1) carbon with a C:N ratio of 20:1 for IPC-P, respectively. The results indicated that the influence of carbon concentration and C:N ratio on fungal growth and sporulation is strain dependent; therefore, consideration for the complexity of nutrient requirements is essential for improving yields of fungal biocontrol agents.

Metalloprobes: Synthesis, Characterization, and Potency of a Novel Gallium(III) Complex in Human Epidermal Carcinoma Cells

PubMed Central

Harpstrite, Scott E.; Prior, Julie; Rath, Nigam P.; Sharma, Vijay

2009-01-01

Multidrug resistance (MDR) mediated by overexpression of the MDR1 gene product, P-glycoprotein (Pgp), represents one of the best characterized barriers to chemotherapeutic treatment in cancer and may be a pivotal factor in progression of Alzheimer’s disease (AD). Thus, agents capable of probing Pgp-mediated transport could be beneficial in biomedical imaging. Herein, we synthesized and structurally characterized a gallium(III) complex of the naphthol-Schiff base ligand (5). The crystal structure revealed octahedral geometry for the metallodrug. Cytotoxicity profiles of 5 were evaluated in KB-3-1 (Pgp−) and KB-8-5 (Pgp+) human epidermal carcinoma cell lines. Compared with an LC50 (the half-maximal cytotoxic concentration) value of 1.93 μM in drug-sensitive (Pgp−) cells, the gallium(III) complex 5 demonstrated an LC50 value > 100 μM in drug-resistant (Pgp+) cells, thus indicating that 5 was recognized by the Pgp as its substrate, thereby extruded from the cells and sequestered away from their cytotoxic targets. Radiolabeled analogues of 5 could be beneficial in noninvasive imaging of Pgp-mediated transport in vivo. PMID:17617464

EPA Science Matters Newsletter: Chemical Warfare Agent Analytical Standards Facilitate Lab Testing (Published November 2013)

EPA Pesticide Factsheets

Learn about the EPA chemists' efforts to develop methods for detecting extremely low concentrations of nerve agents, such as sarin, VX, soman and cyclohexyl sarin, and the blister agent sulfur mustard.

Photoexpulsion of surface-grafted ruthenium complexes and subsequent release of cytotoxic cargos to cancer cells from mesoporous silica nanoparticles.

PubMed

Frasconi, Marco; Liu, Zhichang; Lei, Juying; Wu, Yilei; Strekalova, Elena; Malin, Dmitry; Ambrogio, Michael W; Chen, Xinqi; Botros, Youssry Y; Cryns, Vincent L; Sauvage, Jean-Pierre; Stoddart, J Fraser

2013-08-07

Ruthenium(II) polypyridyl complexes have emerged both as promising probes of DNA structure and as anticancer agents because of their unique photophysical and cytotoxic properties. A key consideration in the administration of those therapeutic agents is the optimization of their chemical reactivities to allow facile attack on the target sites, yet avoid unwanted side effects. Here, we present a drug delivery platform technology, obtained by grafting the surface of mesoporous silica nanoparticles (MSNPs) with ruthenium(II) dipyridophenazine (dppz) complexes. This hybrid nanomaterial displays enhanced luminescent properties relative to that of the ruthenium(II) dppz complex in a homogeneous phase. Since the coordination between the ruthenium(II) complex and a monodentate ligand linked covalently to the nanoparticles can be cleaved under irradiation with visible light, the ruthenium complex can be released from the surface of the nanoparticles by selective substitution of this ligand with a water molecule. Indeed, the modified MSNPs undergo rapid cellular uptake, and after activation with light, the release of an aqua ruthenium(II) complex is observed. We have delivered, in combination, the ruthenium(II) complex and paclitaxel, loaded in the mesoporous structure, to breast cancer cells. This hybrid material represents a promising candidate as one of the so-called theranostic agents that possess both diagnostic and therapeutic functions.

Submicron polycaprolactone particles as a carrier for imaging contrast agent for in vitro applications.

PubMed

Iqbal, Muhammad; Robin, Sophie; Humbert, Philippe; Viennet, Céline; Agusti, Geraldine; Fessi, Hatem; Elaissari, Abdelhamid

2015-12-01

Fluorescent materials have recently attracted considerable attention due to their unique properties and high performance as imaging agent in biomedical fields. Different imaging agents have been encapsulated in order to restrict its delivery to a specific area. In this study, a fluorescent contrast agent was encapsulated for in vitro application by polycaprolactone (PCL) polymer. The encapsulation was performed using modified double emulsion solvent evaporation technique with sonication. Fluorescent nanoparticles (20 nm) were incorporated in the inner aqueous phase of double emulsion. A number of samples were fabricated using different concentrations of fluorescent contrast agent. The contrast agent-containing submicron particle was characterized by a zetasizer for average particle size, SEM and TEM for morphology observations and fluorescence spectrophotometer for encapsulation efficiency. Moreover, contrast agent distribution in the PCL matrix was determined by confocal microscopy. The incorporation of contrast agent in different concentrations did not affect the physicochemical properties of PCL particles and the average size of encapsulated particles was found to be in the submicron range. Copyright © 2015 Elsevier B.V. All rights reserved.

[Epidemiologic diagnostic of nosocomial suppurative-septic infections of Pseudomonas etiology based on intraspecies typing of causative agent].

PubMed

Fel'dblium, I V; Zakharova, Iu A; Nikolaeva, A M; Fedotova, O S

2013-01-01

Scientific justification of optimization of epidemiologic diagnostic of suppurative-septic infection (SSI) caused by Pseudomonas aeruginosa based on comparability of antibiotic sensitivity and beta-lactamase production. Intraspecies typing of 37 P. aeruginosa strains isolated during microbiological monitoring of 106 patients and 131 objects of clinical environment of surgical and obstetrician hospitals by using a complex ofphenotypic and molecular-biological methods including determination of sensitivity to antibiotics by serial dilutions method and PCR-diagnostics with determination of TEM, SHV, CTX, OXA, MBL, VIM genes was performed. P. aeruginosa strains combined into groups by isolation location during studies turned out to be heterogeneous by sensitivity to antibiotics and beta-lactamase production that allowed to form subgroups of strains by focality attribute. Isolates recovered from different SSI foci had significant differences in minimal inhibitory concentration (MIC) reaching 1024 times. MIC parameter within subgroups did not exceed 8 - 16 consequent dilutions. Use of a complex of phenotypic and molecular-biologic methods of causative agent typing including determination of sensitivity to antibiotics by serial dilutions method and evaluation of beta-lactamase production allowed to establish a mechanism of development of SSI epidemic process caused by P. aeruginosa, detect origins and reservoirs of infection in hospital, modes and factors of transmission and reach maximum justification of epidemiologic control and prophylaxis measures of localization of foci of nosocomial infections of pseudomonas etiology.

Partial information, market efficiency, and anomalous continuous phase transition

NASA Astrophysics Data System (ADS)

Yang, Guang; Zheng, Wenzhi; Huang, Jiping

2014-04-01

It is a common belief in economics and social science that if there is more information available for agents to gather in a human system, the system can become more efficient. The belief can be easily understood according to the well-known efficient market hypothesis. In this work, we attempt to challenge this belief by investigating a complex adaptive system, which is modeled by a market-directed resource-allocation game with a directed random network. We conduct a series of controlled human experiments in the laboratory to show the reliability of the model design. As a result, we find that even under a small information concentration, the system can still almost reach the optimal (balanced) state. Furthermore, the ensemble average of the system’s fluctuation level goes through a continuous phase transition. This behavior means that in the second phase if too much information is shared among agents, the system’s stability will be harmed instead, which differs from the belief mentioned above. Also, at the transition point, the ensemble fluctuations of the fluctuation level remain at a low value. This phenomenon is in contrast to the textbook knowledge about continuous phase transitions in traditional physical systems, namely, fluctuations will rise abnormally around a transition point since the correlation length becomes infinite. Thus, this work is of potential value to a variety of fields, such as physics, economics, complexity science, and artificial intelligence.

Cytokines, chemokines, and colony-stimulating factors in human milk: the 1997 update.

PubMed

Garofalo, R P; Goldman, A S

1998-01-01

Epidemiologic studies conducted over the past 30 years to investigate the protective functions of human milk strongly support the notion that breast-feeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult due to its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. Nevertheless, a host of bioactive substances including hormones, growth factors, and immunological factors such as cytokines have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of the immune system. Several different cytokines and chemokines have been discovered in human milk over the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system.

Cytokines in human milk.

PubMed

Garofalo, Roberto

2010-02-01

Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

Fluorescent carbon dots as an efficient siRNA nanocarrier for its interference therapy in gastric cancer cells.

PubMed

Wang, Qing; Zhang, Chunlei; Shen, Guangxia; Liu, Huiyang; Fu, Hualin; Cui, Daxiang

2014-12-30

Fluorescent carbon dots (Cdots) have attracted increasing attention due to their potential applications in sensing, catalysis, and biomedicine. Currently, intensive research has been concentrated on the synthesis and imaging-guided therapy of these benign photoluminescent materials. Meanwhile, Cdots have been explored as nonviral vector for nucleic acid or drug delivery by chemical modification on purpose. We have developed a microwave assisted one-step synthesis of Cdots with citric acid as carbon source and tryptophan (Trp) as both nitrogen source and passivation agent. The Cdots with uniform size show superior water solubility, excellent biocompatibility, and high quantum yield. Afterwards, the PEI (polyethylenimine)-adsorbed Cdots nanoparticles (Cdots@PEI) were applied to deliver Survivin siRNA into human gastric cancer cell line MGC-803. The results have confirmed the nanocarrier exhibited excellent biocompatibility and a significant increase in cellular delivery of siRNA, inducing efficient knockdown for Survivin protein to 6.1%. In addition, PEI@Cdots complexes mediated Survivin silencing, the arrested cell cycle progression in G1 phase as well as cell apoptosis was observed. The Cdots-based and PEI-adsorbed complexes both as imaging agents and siRNA nanocarriers have been developed for Survivin siRNA delivery. And the results indicate that Cdots-based nanocarriers could be utilized in a broad range of siRNA delivery systems for cancer therapy.

Controlling collective dynamics in complex minority-game resource-allocation systems

NASA Astrophysics Data System (ADS)

Zhang, Ji-Qiang; Huang, Zi-Gang; Dong, Jia-Qi; Huang, Liang; Lai, Ying-Cheng

2013-05-01

Resource allocation takes place in various kinds of real-world complex systems, such as traffic systems, social services institutions or organizations, or even ecosystems. The fundamental principle underlying complex resource-allocation dynamics is Boolean interactions associated with minority games, as resources are generally limited and agents tend to choose the least used resource based on available information. A common but harmful dynamical behavior in resource-allocation systems is herding, where there are time intervals during which a large majority of the agents compete for a few resources, leaving many other resources unused. Accompanying the herd behavior is thus strong fluctuations with time in the number of resources being used. In this paper, we articulate and establish that an intuitive control strategy, namely pinning control, is effective at harnessing the herding dynamics. In particular, by fixing the choices of resources for a few agents while leaving the majority of the agents free, herding can be eliminated completely. Our investigation is systematic in that we consider random and targeted pinning and a variety of network topologies, and we carry out a comprehensive analysis in the framework of mean-field theory to understand the working of control. The basic philosophy is then that, when a few agents waive their freedom to choose resources by receiving sufficient incentives, the majority of the agents benefit in that they will make fair, efficient, and effective use of the available resources. Our work represents a basic and general framework to address the fundamental issue of fluctuations in complex dynamical systems with significant applications to social, economical, and political systems.

Rich or poor: Who should pay higher tax rates?

NASA Astrophysics Data System (ADS)

Murilo Castro de Oliveira, Paulo

2017-08-01

A dynamic agent model is introduced with an annual random wealth multiplicative process followed by taxes paid according to a linear wealth-dependent tax rate. If poor agents pay higher tax rates than rich agents, eventually all wealth becomes concentrated in the hands of a single agent. By contrast, if poor agents are subject to lower tax rates, the economic collective process continues forever.

Evaluating the antimicrobial activity of Nisin, Lysozyme and Ethylenediaminetetraacetate incorporated in starch based active food packaging film.

PubMed

Bhatia, Sugandha; Bharti, Anoop

2015-06-01

The pleothera of micro organisms obtained from contaminated food cultured in a starch broth was effectively tested against antibacterial agents, i.e. nisin, lysozyme and chelating agent EDTA. A variety of combination treatments of these antimicrobial agents and their incorporation in Starch based active packaging film according to their permissibility standards was done. 4 variables of Nisin concentration (ranging from 0 to 750 IU/ml), 3 variables of lysozyme concentration (ranging from 0 to 500 IU/ml) and 3 variables of EDTA concentration from (0 to 20 μM) were chosen. Bacterial inhibition by combination of different levels of different factors without antimicrobial films was evaluated using a liquid incubation method. The samples were assayed for turbidity at interval of 2, 4 and 24 h to check effectiveness of combined effects of antimicrobial agents which proved a transitory bactericidal effect for short incubation times. Zone of Inhibition was observed in the antimicrobial films prepared by agar diffusion method. Statistical analysis of experimental data for their antimicrobial spectrum was carried out by multi regression analysis and ANOVA using Design-Expert software to plot the final equation in terms of coded factors as antimicrobial agents. The experimental data indicated that the model was highly significant. Results were also evaluated graphically using response surface showing interactions between two factors, keeping other factor fixed at values at the center of domain. Synergy was also determined among antibacterial agents using the fractional inhibitory concentration (FIC) index which was observed to be 0.56 supporting the hypothesis that nisin and EDTA function as partial synergistically. The presented work aimed to screen in quick fashion the combinatorial effect of three antimicrobial agents and evaluating their efficacy in anti microbial film development.

An attempt to evaluate the effect of vitamin K3 using as an enhancer of anticancer agents.

PubMed

Matzno, Sumio; Yamaguchi, Yuka; Akiyoshi, Takeshi; Nakabayashi, Toshikatsu; Matsuyama, Kenji

2008-06-01

The possibility of vitamin K3 (VK3) as an anticancer agent was assessed. VK3 dose-dependently diminished the cell viability (measured as esterase activity) with IC50 of 13.7 microM and Hill coefficient of 3.1 in Hep G2 cells. It also decreased the population of S phase and arrested cell cycle in the G2/M phase in a dose-dependent manner. G2/M arrest was regulated by the increment of cyclin A/cdk1 and cyclin A/cdk2 complex, and contrasting cyclin B/cdk1 complex decrease. Finally, combined application demonstrated that VK3 significantly enhanced the cytotoxicity of etoposide, a G2 phase-dependent anticancer agent, whereas it reduced the cytotoxic activity of irinotecan, a S phase-dependent agent. These findings suggest that VK3 induces G2/M arrest by inhibition of cyclin B/cdk1 complex formation, and is thus useful as an enhancer of G2 phase-dependent drugs in hepatic cancer chemotherapy.

Facile and green synthesis of highly stable L-cysteine functionalized copper nanoparticles

NASA Astrophysics Data System (ADS)

Kumar, Nikhil; Upadhyay, Lata Sheo Bachan

2016-11-01

A simple eco-friendly method for L-cysteine capped copper nanoparticles (CCNPs) synthesis in aqueous solution has been developed. Glucose and L-cysteine were used as reducing agent and capping/functionalizing agent, respectively. Different parameters such as capping agent concentration, pH, reaction temperature, and reducing agent concentration were optimized during the synthesis. The L-cysteine capped copper nanoparticle were characterized by ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, Particle size and zeta potential analyser, and high resolution transmission electron microscopy. Spherical shaped cysteine functionalized/capped copper nanoparticles with an average size of 40 nm were found to be highly stable at room temperature (RT) for a period of 1 month

Multichannel imaging to quantify four classes of pharmacokinetic distribution in tumors.

PubMed

Bhatnagar, Sumit; Deschenes, Emily; Liao, Jianshan; Cilliers, Cornelius; Thurber, Greg M

2014-10-01

Low and heterogeneous delivery of drugs and imaging agents to tumors results in decreased efficacy and poor imaging results. Systemic delivery involves a complex interplay of drug properties and physiological factors, and heterogeneity in the tumor microenvironment makes predicting and overcoming these limitations exceptionally difficult. Theoretical models have indicated that there are four different classes of pharmacokinetic behavior in tissue, depending on the fundamental steps in distribution. In order to study these limiting behaviors, we used multichannel fluorescence microscopy and stitching of high-resolution images to examine the distribution of four agents in the same tumor microenvironment. A validated generic partial differential equation model with a graphical user interface was used to select fluorescent agents exhibiting these four classes of behavior, and the imaging results agreed with predictions. BODIPY-FL exhibited higher concentrations in tissue with high blood flow, cetuximab gave perivascular distribution limited by permeability, high plasma protein and target binding resulted in diffusion-limited distribution for Hoechst 33342, and Integrisense 680 was limited by the number of binding sites in the tissue. Together, the probes and simulations can be used to investigate distribution in other tumor models, predict tumor drug distribution profiles, and design and interpret in vivo experiments. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Extraction-spectrophotometric determination of tris(2-chloroethyl)amine using phthaleins.

PubMed

Rozsypal, Tomas; Halamek, Emil

2017-06-01

Procedures for the extraction-spectrophotometric determination of tris(2-chloroethyl)amine, an alkylating agent known as a drug as well as a chemical warfare agent (nitrogen mustard HN-3), with 7 acid-base indicators of a triphenylmethane lactone type, phthaleins, were developed. Representatives of phthaleins without an oxygen bridge (thymolphthalein, o-cresolphthalein, naphtholphthalein) and with an oxygen bridge (fluorescein, 2',7'-dichlorofluorescein, eosin B and eosin Y) were used. The methods were based on the formation of ion pair complexes. Chloroform was used as a non-polar solvent for an extraction. The conditions to determine were optimized for the optimal pH of the buffer and the concentration of a phthalein as a reagent. The dependence on the reaction time in a water phase and the stoichiometry of extraction products were studied. The detection limits and the limits of the determination of separate procedures and conditional extraction constants were determined. Comparison with the spectrophotometric method of the group determination of alkyl halides and acyl halides using alkaline ethanol-water solution of thymolphthalein, the so-called T-135 agent, was conducted. While studying the selectivity, the possible interference of bis(2-chloroethyl)sulphide and 3 nitrogen mustards in the proposed procedures were verified. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Copper complexes as a source of redox active MRI contrast agents.

PubMed

Dunbar, Lynsey; Sowden, Rebecca J; Trotter, Katherine D; Taylor, Michelle K; Smith, David; Kennedy, Alan R; Reglinski, John; Spickett, Corinne M

2015-10-01

The study reports an advance in designing copper-based redox sensing MRI contrast agents. Although the data demonstrate that copper(II) complexes are not able to compete with lanthanoids species in terms of contrast, the redox-dependent switch between diamagnetic copper(I) and paramagnetic copper(II) yields a novel redox-sensitive contrast moiety with potential for reversibility.

Human Aided Reinforcement Learning in Complex Environments

DTIC Science & Technology

learn to solve tasks through a trial -and- error process. As an agent takes ...task faster andmore accurately, a human expert can be added to the system to guide an agent in solving the task. This project seeks to expand on current...theenvironment, which works particularly well for reactive tasks . In more complex tasks , these systems do not work as intended. The manipulation

Formulation and method for preparing gels comprising hydrous hafnium oxide

DOEpatents

Collins, Jack L; Hunt, Rodney D; Montgomery, Frederick C

2013-08-06

Formulations useful for preparing hydrous hafnium oxide gels contain a metal salt including hafnium, an acid, an organic base, and a complexing agent. Methods for preparing gels containing hydrous hafnium oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including hafnium, an acid, an organic base, and a complexing agent.

Preparation of a Cobalt(II) Cage: An Undergraduate Laboratory Experiment That Produces a ParaSHIFT Agent for Magnetic Resonance Spectroscopy

ERIC Educational Resources Information Center

Burns, Patrick J.; Tsitovich, Pavel B.; Morrow, Janet R.

2016-01-01

Laboratory experiments that demonstrate the effect of paramagnetic complexes on chemical shifts and relaxation times of protons are a useful way to introduce magnetic resonance spectroscopy (MRS) probes or magnetic resonance imaging (MRI) contrast agents. In this undergraduate inorganic chemistry experiment, a paramagnetic Co(II) cage complex is…

Hyaluronate tethered, "smart" multiwalled carbon nanotubes for tumor-targeted delivery of doxorubicin.

PubMed

Datir, Satyajit R; Das, Manasmita; Singh, Raman Preet; Jain, Sanyog

2012-11-21

The present study reports the optimized synthesis, physicochemical characterization, and biological evaluation of a novel, multiwalled carbon nanotube-hyaluronic acid (MWCNT-HA) conjugate, complexed with an anticancer agent, Doxorubicin (DOX) via π-π stacking interaction. The therapeutic conjugate was concomitantly labeled with a near-infrared fluorescent dye, Alexa-Flour-647 (AF-647), and radiotracer Technetium-99m ((99m)Tc) to track its whereabouts both in vitro and in vivo via optical and scintigraphic imaging techniques. Covalent functionalization of MWCNTs with HA facilitated their internalization into human lung adenocarcinoma, A549 cells via hyaluronan receptors (HR) mediated endocytosis. Internalized nanotubes showed lysosomal trafficking, followed by low pH-triggered DOX release under endolysosomal conditions. Consequently, DOX-loaded HA-MWCNTs exhibited 3.2 times higher cytotoxicity and increased apoptotic activity than free DOX in equivalent concentrations. Organ distribution studies in Ehlrich ascites tumor (EAT) bearing mice model indicated that tumor specific localization of (99m)Tc-MWCNT-HA-DOX is significantly higher than both free drug and nontargeted MWCNTs. Pharmacodynamic studies in chemically breast-cancer-induced rats showed that the tumor-growth inhibitory effect of HA-MWCNT-DOX was 5 times higher than free DOX in equivalent concentration. DOX delivered through HA-MWCNTs was devoid of any detectable cardiotoxity, hepatotoxicity, or nephrotoxicity. All these promising attributes make HA-MWCNTs a "smart" platform for tumor-targeted delivery of anticancer agents.

Reaction of a chemotherapeutic agent, 6-mercaptopurine, with a direct-acting, electrophilic carcinogen, benzo[a]pyrene-7,8-diol 9,10-epoxide.

PubMed

MacLeod, M C; Stewart, E; Daylong, A; Lew, L K; Evans, F E

1991-01-01

The chemotherapeutic agent 6-mercaptopurine (6-MP) has been shown to react covalently with the ultimate carcinogenic metabolite of benzo[a]pyrene, 7-r,8-t-dihydroxy-9-t,10-t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), in aqueous solution, forming a single adduct. NMR studies of the HPLC-purified product were consistent with its identification as 10(S)-(6'-mercaptopurinyl)-7,8,9-trihydroxy-7,8,9,10- tetrahydrobenzo[a]pyrene. Reaction kinetics were analyzed by using both HPLC separation of the products formed and a spectrophotometric assay for adduct formation. A simple model in which direct reaction between 6-MP and BPDE takes place without formation of a physical complex was found to adequately predict the dependence of product ratios on 6-MP concentration. Variations in the observed rate constant for this reaction with changes in temperature, pH, and buffer concentration were determined and compared to the effects of these variables on the observed rate constant for BPDE hydrolysis. In each case, the processes were affected quite differently, suggesting that different rate-determining steps are involved. The data suggest that the reaction mechanism involves SN2 attack of the anion of 6-MP, formed by ionization of the sulfhydryl group, on carbon 10 of BPDE, resulting in a trans-9,10 reaction product.

Drug release control and system understanding of sucrose esters matrix tablets by artificial neural networks.

PubMed

Chansanroj, Krisanin; Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele

2011-10-09

Artificial neural networks (ANNs) were applied for system understanding and prediction of drug release properties from direct compacted matrix tablets using sucrose esters (SEs) as matrix-forming agents for controlled release of a highly water soluble drug, metoprolol tartrate. Complexity of the system was presented through the effects of SE concentration and tablet porosity at various hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both effects contributed to release behaviors especially in the system containing hydrophilic SEs where swelling phenomena occurred. A self-organizing map neural network (SOM) was applied for visualizing interrelation among the variables and multilayer perceptron neural networks (MLPs) were employed to generalize the system and predict the drug release properties based on HLB value and concentration of SEs and tablet properties, i.e., tablet porosity, volume and tensile strength. Accurate prediction was obtained after systematically optimizing network performance based on learning algorithm of MLP. Drug release was mainly attributed to the effects of SEs, tablet volume and tensile strength in multi-dimensional interrelation whereas tablet porosity gave a small impact. Ability of system generalization and accurate prediction of the drug release properties proves the validity of SOM and MLPs for the formulation modeling of direct compacted matrix tablets containing controlled release agents of different material properties. Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical warfare agents.

PubMed

Kuca, Kamil; Pohanka, Miroslav

2010-01-01

Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

The Influence of Lactic Acid Concentration on the Separation of Light Rare Earth Elements by Continuous Liquid-Liquid Extraction with 2-Ethylhexyl Phosphonic Acid Mono-2-ethylhexyl Ester

NASA Astrophysics Data System (ADS)

de Carvalho Gomes, Rafael; Seruff, Luciana Amaral; Scal, Maira Labanca Waineraich; Vera, Ysrael Marrero

2018-02-01

The separation of rare earth elements (REEs) using solvent extraction adding complexing agents appears to be an alternative to saponification of the extractant. We evaluated the effect of lactic acid concentration on didymium (praseodymium and neodymium) and lanthanum extraction with 2-ethylhexyl phosphonic acid mono-2-ethyl hexyl ester [HEH(EHP)] as extractant. First, we investigated in batch experiments the separation of lanthanum (La) and didymium (Pr and Nd) using McCabe-Thiele diagrams to estimate the number of extraction stages when the feed solution was or was not conditioned with lactic acid. Additionally, we conducted continuous liquid-liquid extraction experiments and evaluated the influence of lactic acid concentration on the REE extraction and separation. The tests showed that the extraction percentage of REEs and the separation factor Pr/La increased when the lactic acid concentration increased, but the didymium purity decreased. Lanthanum, praseodymium, and neodymium extraction rate were 23.0, 89.7, and 99.2 pct, respectively, with 1:1 aqueous/organic volume flow rate and feed solution doped with 0.52 mol L-1 lactic acid. The highest didymium purity reached was 92.0 pct with 0.26 mol L-1 lactic acid concentration.

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

Tiger, G.; Fowler, C.J.

The calcium and potassium ion dependency of the inositol phospholipid breakdown response to stimulatory agents has been investigated in rat cerebral cortical miniprisms. The calcium channel agonist BAY K-8644 potentiated the response to carbachol at 6 mM K{sup +} when Ca{sup 2+}-free, but not when 2.52 mM Ca{sup 2+} assay buffer was used. In Ca{sup 2+}-free buffer, verapamil inhibited the response to carbachol at both 6 and 18 mM K{sup +} but higher concentrations were needed when 2.52 mM Ca{sup 2+} was used. At these higher concentrations, however, verapamil inhibited the binding of 2 nM ({sup 3}H)pirenzepine to muscarinic recognitionmore » sites. N-Methyl-D-Aspartate (NMDA) significantly reduced the basal phosphoinositide breakdown rate at 18 mM K{sup +} at 1.3 mM Ca{sup 2+}, but was without effect on the basal rate at other K{sup +} and Ca{sup 2+} concentrations. In the presence of NMDA or quisqualate, the responses to carbachol were reduced, the degree of reduction showing a complex dependency upon the assay K{sup +} and Ca{sup 2+} concentrations used. These results indicate that the inositol phospholipid breakdown response to carbachol in cerebral cortical miniprisms can be modulated in a manner dependent upon the extracellular calcium and potassium concentrations used.« less

Physical characteristics of lanthanide complexes that act as magnetization transfer (MT) contrast agents

NASA Astrophysics Data System (ADS)

Zhang, Shanrong; Sherry, A. Dean

2003-02-01

Rapid water exchange is normally considered a prerequisite for efficient Gd3+-based MRI contrast agents. Yet recent measures of exchange rates in some Gd3+ complexes have shown that water exchange can become limiting when such complexes are attached to larger macromolecular structures. A new class of lanthanide complexes that display unusually slow water exchange (bound water lifetimes (τM298) > 10 μs) has recently been reported. This apparent disadvantage may be taken advantage of by switching the metal ion from gadolinium(III) to a lanthanide that shifts the bound water resonance substantially away from bulk water. Given appropriate water exchange kinetics, one can then alter the intensity of the bulk water signal by selective presaturation of this highly shifted, Ln3+-bound water resonance. This provides the basis of a new method to alter MR image contrast in tissue. We have synthesized a variety of DOTA-tetra(amide) ligands to evaluate as potential magnetization transfer (MT) contrast agents and found that the bound water lifetimes in these complexes are sensitive to both ligand structure (a series of Eu3+ complexes have τM298 values that range from 1 to 1300 μs) and the identity of the paramagnetic Ln3+ cation (from 3 to 800 μs for a single ligand). This demonstrates that it may be possible either to fine-tune the ligand structure or to select proper lanthanide cation to create an optimal MT agent for any clinical imaging field.

Fuselets: an agent based architecture for fusion of heterogeneous information and data

NASA Astrophysics Data System (ADS)

Beyerer, Jürgen; Heizmann, Michael; Sander, Jennifer

2006-04-01

A new architecture for fusing information and data from heterogeneous sources is proposed. The approach takes criminalistics as a model. In analogy to the work of detectives, who attempt to investigate crimes, software agents are initiated that pursue clues and try to consolidate or to dismiss hypotheses. Like their human pendants, they can, if questions beyond their competences arise, consult expert agents. Within the context of a certain task, region, and time interval, specialized operations are applied to each relevant information source, e.g. IMINT, SIGINT, ACINT,..., HUMINT, data bases etc. in order to establish hit lists of first clues. Each clue is described by its pertaining facts, uncertainties, and dependencies in form of a local degree-of-belief (DoB) distribution in a Bayesian sense. For each clue an agent is initiated which cooperates with other agents and experts. Expert agents support to make use of different information sources. Consultations of experts, capable to access certain information sources, result in changes of the DoB of the pertaining clue. According to the significance of concentration of their DoB distribution clues are abandoned or pursued further to formulate task specific hypotheses. Communications between the agents serve to find out whether different clues belong to the same cause and thus can be put together. At the end of the investigation process, the different hypotheses are evaluated by a jury and a final report is created that constitutes the fusion result. The approach proposed avoids calculating global DoB distributions by adopting a local Bayesian approximation and thus reduces the complexity of the exact problem essentially. Different information sources are transformed into DoB distributions using the maximum entropy paradigm and considering known facts as constraints. Nominal, ordinal and cardinal quantities can be treated within this framework equally. The architecture is scalable by tailoring the number of agents according to the available computer resources, to the priority of tasks, and to the maximum duration of the fusion process. Furthermore, the architecture allows cooperative work of human and automated agents and experts, as long as not all subtasks can be accomplished automatically.

QUESP and QUEST revisited - fast and accurate quantitative CEST experiments.

PubMed

Zaiss, Moritz; Angelovski, Goran; Demetriou, Eleni; McMahon, Michael T; Golay, Xavier; Scheffler, Klaus

2018-03-01

Chemical exchange saturation transfer (CEST) NMR or MRI experiments allow detection of low concentrated molecules with enhanced sensitivity via their proton exchange with the abundant water pool. Be it endogenous metabolites or exogenous contrast agents, an exact quantification of the actual exchange rate is required to design optimal pulse sequences and/or specific sensitive agents. Refined analytical expressions allow deeper insight and improvement of accuracy for common quantification techniques. The accuracy of standard quantification methodologies, such as quantification of exchange rate using varying saturation power or varying saturation time, is improved especially for the case of nonequilibrium initial conditions and weak labeling conditions, meaning the saturation amplitude is smaller than the exchange rate (γB 1  < k). The improved analytical 'quantification of exchange rate using varying saturation power/time' (QUESP/QUEST) equations allow for more accurate exchange rate determination, and provide clear insights on the general principles to execute the experiments and to perform numerical evaluation. The proposed methodology was evaluated on the large-shift regime of paramagnetic chemical-exchange-saturation-transfer agents using simulated data and data of the paramagnetic Eu(III) complex of DOTA-tetraglycineamide. The refined formulas yield improved exchange rate estimation. General convergence intervals of the methods that would apply for smaller shift agents are also discussed. Magn Reson Med 79:1708-1721, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Methylene blue microbubbles as a model dual-modality contrast agent for ultrasound and activatable photoacoustic imaging

NASA Astrophysics Data System (ADS)

Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L.; Leung, Ben Y. C.; Goertz, David E.; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F.; Kim, Chulhong

2014-01-01

Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

Methylene blue microbubbles as a model dual-modality contrast agent for ultrasound and activatable photoacoustic imaging.

PubMed

Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L; Leung, Ben Y C; Goertz, David E; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F; Kim, Chulhong

2014-01-01

Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

At clinically relevant concentrations the anaesthetic/amnesic thiopental but not the anticonvulsant phenobarbital interferes with hippocampal sharp wave-ripple complexes

PubMed Central

Papatheodoropoulos, Costas; Sotiriou, Evangelos; Kotzadimitriou, Dimitrios; Drimala, Panagiota

2007-01-01

Background Many sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms. Sharp-wave ripple (SPW-R) complexes are network activity thought to represent the neuronal substrate for information transfer from the hippocampal to neocortical circuits, contributing to the explicit memory consolidation. In this study we examined and compared the actions of two barbiturates with distinct amnesic actions, the general anesthetic thiopental and the anticonvulsant phenobarbital, on in vitro SPW-R activity. Results Using an in vitro model of SPW-R activity we found that thiopental (50–200 μM) significantly and concentration-dependently reduced the incidence of SPW-R events (it increased the inter-event period by 70–430 %). At the concentration of 25 μM, which clinically produces mild sedation and explicit memory impairment, thiopental significantly reduced the quantity of ripple oscillation (it reduced the number of ripples and the duration of ripple episodes by 20 ± 5%, n = 12, P < 0.01), and suppressed the rhythmicity of SPWs by 43 ± 15% (n = 6, P < 0.05). The drug disrupted the synchrony of SPWs within the CA1 region at 50 μM (by 19 ± 12%; n = 5, P < 0.05). Similar effects of thiopental were observed at higher concentrations. Thiopental did not affect the frequency of ripple oscillation at any of the concentrations tested (10–200 μM). Furthermore, the drug significantly prolonged single SPWs at concentrations ≥50 μM (it increased the half-width and the duration of SPWs by 35–90 %). Thiopental did not affect evoked excitatory synaptic potentials and its results on SPW-R complexes were also observed under blockade of NMDA receptors. Phenobarbital significantly accelerated SPWs at 50 and 100 μM whereas it reduced their rate at 200 and 400 μM. Furthermore, it significantly prolonged SPWs, reduced their synchrony and reduced the quantity of ripples only at the clinically very high concentration of 400 μM, reported to affect memory. Conclusion We hypothesize that thiopental, by interfering with SPW-R activity, through enhancement of the GABAA receptor-mediated transmission, affects memory processes which involve hippocampal circuit activation. The quantity but not the frequency of ripple oscillation was affected by the drug. PMID:17672909

Quantum Speedup for Active Learning Agents

NASA Astrophysics Data System (ADS)

Paparo, Giuseppe Davide; Dunjko, Vedran; Makmal, Adi; Martin-Delgado, Miguel Angel; Briegel, Hans J.

2014-07-01

Can quantum mechanics help us build intelligent learning agents? A defining signature of intelligent behavior is the capacity to learn from experience. However, a major bottleneck for agents to learn in real-life situations is the size and complexity of the corresponding task environment. Even in a moderately realistic environment, it may simply take too long to rationally respond to a given situation. If the environment is impatient, allowing only a certain time for a response, an agent may then be unable to cope with the situation and to learn at all. Here, we show that quantum physics can help and provide a quadratic speedup for active learning as a genuine problem of artificial intelligence. This result will be particularly relevant for applications involving complex task environments.

Casuist BDI-Agent: A New Extended BDI Architecture with the Capability of Ethical Reasoning

NASA Astrophysics Data System (ADS)

Honarvar, Ali Reza; Ghasem-Aghaee, Nasser

Since the intelligent agent is developed to be cleverer, more complex, and yet uncontrollable, a number of problems have been recognized. The capability of agents to make moral decisions has become an important question, when intelligent agents have developed more autonomous and human-like. We propose Casuist BDI-Agent architecture which extends the power of BDI architecture. Casuist BDI-Agent architecture combines CBR method in AI and bottom up casuist approach in ethics in order to add capability of ethical reasoning to BDI-Agent.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.N.; Xu, J.

1997-04-29

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth N.; Xu, Jide

1997-01-01

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of said chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to said 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities.

Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

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

Fatimah, Soja Siti, E-mail: soja-sf@upi.edu; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jl. Raya Bandung-Sumedang, Km. 21, Jatinangor; Bahti, Husein H.

2016-02-08

The use of dialkyldithiocarbamates as chelating agents of transition metals have been developing for decades. Many chelating agents have been synthesized and used in the extraction of the metals. Studies on particular aspects of extraction of the metals, such as the effect of increasing hydrophobicity of chelating agents on the effectiveness of the extraction, have been done. However, despite the many studies on the synthesis and applications of this type of chelating agents, interests in the aspect of molecular structure of the synthesized ligands and of their complexes, have been limited. This study aimed at synthesizing and characterizing dihexylthiocarbamate, andmore » using the ligand for the extraction of gold III). Characterization of the ligand and of its metal complex were done by using elemental analysis, DTG, and spectroscopic methods to include NMR, ({sup 1}H, and {sup 13}C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.« less

Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

NASA Astrophysics Data System (ADS)

Fatimah, Soja Siti; Bahti, Husein H.; Hastiawan, Iwan; Permanasari, Anna

2016-02-01

The use of dialkyldithiocarbamates as chelating agents of transition metals have been developing for decades. Many chelating agents have been synthesized and used in the extraction of the metals. Studies on particular aspects of extraction of the metals, such as the effect of increasing hydrophobicity of chelating agents on the effectiveness of the extraction, have been done. However, despite the many studies on the synthesis and applications of this type of chelating agents, interests in the aspect of molecular structure of the synthesized ligands and of their complexes, have been limited. This study aimed at synthesizing and characterizing dihexylthiocarbamate, and using the ligand for the extraction of gold III). Characterization of the ligand and of its metal complex were done by using elemental analysis, DTG, and spectroscopic methods to include NMR, (1H, and 13C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.

Incremental learning of skill collections based on intrinsic motivation

PubMed Central

Metzen, Jan H.; Kirchner, Frank

2013-01-01

Life-long learning of reusable, versatile skills is a key prerequisite for embodied agents that act in a complex, dynamic environment and are faced with different tasks over their lifetime. We address the question of how an agent can learn useful skills efficiently during a developmental period, i.e., when no task is imposed on him and no external reward signal is provided. Learning of skills in a developmental period needs to be incremental and self-motivated. We propose a new incremental, task-independent skill discovery approach that is suited for continuous domains. Furthermore, the agent learns specific skills based on intrinsic motivation mechanisms that determine on which skills learning is focused at a given point in time. We evaluate the approach in a reinforcement learning setup in two continuous domains with complex dynamics. We show that an intrinsically motivated, skill learning agent outperforms an agent which learns task solutions from scratch. Furthermore, we compare different intrinsic motivation mechanisms and how efficiently they make use of the agent's developmental period. PMID:23898265

Reinforcement learning agents providing advice in complex video games

NASA Astrophysics Data System (ADS)

Taylor, Matthew E.; Carboni, Nicholas; Fachantidis, Anestis; Vlahavas, Ioannis; Torrey, Lisa

2014-01-01

This article introduces a teacher-student framework for reinforcement learning, synthesising and extending material that appeared in conference proceedings [Torrey, L., & Taylor, M. E. (2013)]. Teaching on a budget: Agents advising agents in reinforcement learning. {Proceedings of the international conference on autonomous agents and multiagent systems}] and in a non-archival workshop paper [Carboni, N., &Taylor, M. E. (2013, May)]. Preliminary results for 1 vs. 1 tactics in StarCraft. {Proceedings of the adaptive and learning agents workshop (at AAMAS-13)}]. In this framework, a teacher agent instructs a student agent by suggesting actions the student should take as it learns. However, the teacher may only give such advice a limited number of times. We present several novel algorithms that teachers can use to budget their advice effectively, and we evaluate them in two complex video games: StarCraft and Pac-Man. Our results show that the same amount of advice, given at different moments, can have different effects on student learning, and that teachers can significantly affect student learning even when students use different learning methods and state representations.

Design of a multi-agent hydroeconomic model to simulate a complex human-water system: Early insights from the Jordan Water Project

NASA Astrophysics Data System (ADS)

Yoon, J.; Klassert, C. J. A.; Lachaut, T.; Selby, P. D.; Knox, S.; Gorelick, S.; Rajsekhar, D.; Tilmant, A.; Avisse, N.; Harou, J. J.; Gawel, E.; Klauer, B.; Mustafa, D.; Talozi, S.; Sigel, K.

2015-12-01

Our work focuses on development of a multi-agent, hydroeconomic model for purposes of water policy evaluation in Jordan. The model adopts a modular approach, integrating biophysical modules that simulate natural and engineered phenomena with human modules that represent behavior at multiple levels of decision making. The hydrologic modules are developed using spatially-distributed groundwater and surface water models, which are translated into compact simulators for efficient integration into the multi-agent model. For the groundwater model, we adopt a response matrix method approach in which a 3-dimensional MODFLOW model of a complex regional groundwater system is converted into a linear simulator of groundwater response by pre-processing drawdown results from several hundred numerical simulation runs. Surface water models for each major surface water basin in the country are developed in SWAT and similarly translated into simple rainfall-runoff functions for integration with the multi-agent model. The approach balances physically-based, spatially-explicit representation of hydrologic systems with the efficiency required for integration into a complex multi-agent model that is computationally amenable to robust scenario analysis. For the multi-agent model, we explicitly represent human agency at multiple levels of decision making, with agents representing riparian, management, supplier, and water user groups. The agents' decision making models incorporate both rule-based heuristics as well as economic optimization. The model is programmed in Python using Pynsim, a generalizable, open-source object-oriented code framework for modeling network-based water resource systems. The Jordan model is one of the first applications of Pynsim to a real-world water management case study. Preliminary results from a tanker market scenario run through year 2050 are presented in which several salient features of the water system are investigated: competition between urban and private farmer agents, the emergence of a private tanker market, disparities in economic wellbeing to different user groups caused by unique supply conditions, and response of the complex system to various policy interventions.

Computational memory architectures for autobiographic agents interacting in a complex virtual environment: a working model

NASA Astrophysics Data System (ADS)

Ho, Wan Ching; Dautenhahn, Kerstin; Nehaniv, Chrystopher

2008-03-01

In this paper, we discuss the concept of autobiographic agent and how memory may extend an agent's temporal horizon and increase its adaptability. These concepts are applied to an implementation of a scenario where agents are interacting in a complex virtual artificial life environment. We present computational memory architectures for autobiographic virtual agents that enable agents to retrieve meaningful information from their dynamic memories which increases their adaptation and survival in the environment. The design of the memory architectures, the agents, and the virtual environment are described in detail. Next, a series of experimental studies and their results are presented which show the adaptive advantage of autobiographic memory, i.e. from remembering significant experiences. Also, in a multi-agent scenario where agents can communicate via stories based on their autobiographic memory, it is found that new adaptive behaviours can emerge from an individual's reinterpretation of experiences received from other agents whereby higher communication frequency yields better group performance. An interface is described that visualises the memory contents of an agent. From an observer perspective, the agents' behaviours can be understood as individually structured, and temporally grounded, and, with the communication of experience, can be seen to rely on emergent mixed narrative reconstructions combining the experiences of several agents. This research leads to insights into how bottom-up story-telling and autobiographic reconstruction in autonomous, adaptive agents allow temporally grounded behaviour to emerge. The article concludes with a discussion of possible implications of this research direction for future autobiographic, narrative agents.

Mechanism of triclosan toxicity: Mitochondrial dysfunction including complex II inhibition, superoxide release and uncoupling of oxidative phosphorylation.

PubMed

Teplova, Vera V; Belosludtsev, Konstantin N; Kruglov, Alexey G

2017-06-05

Triclosan (5-chloro-2'-(2,4-dichlorophenoxy)phenol), a widely used antibacterial agent, exerts adverse effects on the organism of mammals. Recent research reviled that triclosan at low micromolar concentrations causes mitochondrial dysfunction in many cell types, but the mechanisms of its effect are not fully understood. Here we show that exposure to triclosan disrupted membrane potential, prevented the calcium uptake-driven high-amplitude mitochondrial swelling, stimulated the respiration in the presence of complex I substrates, and suppressed the ADP-stimulated respiration in the presence of complex II substrate, succinate. Triclosan directly inhibited complex II activity. Similar to the complex II inhibitor thenoyltrifluoroacetone, triclosan induced the oxidation of the cytochromes b566 and b562 and caused the release of mitochondrial superoxide. Opposite to thenoyltrifluoroacetone, triclosan increased superoxide release synergistically with myxothiazol but not with antimycin A, indicating different topology of superoxide-producing sites. We concluded that triclosan is unique by its capability of acting as both a protonophore and an unusual complex II inhibitor, which interferes with the mitochondrial respiration by blocking the electron transfer between ubiquinone at the Q d -binding site and heme b. Our data can provide an insight into the mechanisms of the carcinogenic effect of triclosan in the liver and other tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

Symposium on Toxic Substance Control: Decontamination, April 22 - 24, 1980, Columbus, Ohio.

DTIC Science & Technology

1981-06-01

standard decontaminants is used. TABLE 1. Standard Chemical Decontaminants Decontaminant Agents Used On STB Blister and nerve agents DS-2 All chemical... agents M258 Kit Sodium Hydroxide, Ethanol, G-Series nerve agents Phenol, Water Chloramine B, ZnCI2, Blister ana V-Series Ethanol, Water nerve agents A...is a point source alarm that actively samples ambient air and reacts to low concentrations of nerve agents . The M-8 alarm detector also detects several

Factors Affecting the Extraction of Intact Ribonucleic Acid from Plant Tissues Containing Interfering Phenolic Compounds

PubMed Central

Newbury, H. John; Possingham, John V.

1977-01-01

Using conventional methods it is impossible to extract RNA as uncomplexed intact molecules from the leaves of grapevines (Vitis vinifera L.) and from a number of woody perennial species that contain high levels of reactive phenolic compounds. A procedure involving the use of high concentrations of the chaotropic agent sodium perchlorate prevents the binding of phenolic compounds to RNA during extraction. Analyses of the phenolics present in plant tissues used in these experiments indicate that there is a poor correlation between the total phenolic content and the complexing of RNA. However, qualitative analyses suggest that proanthocyanidins are involved in the tanning of RNA during conventional extractions. PMID:16660134

Turning Bone Morphogenetic Protein 2 (BMP2) On and Off in Mesenchymal Cells†

PubMed Central

Rogers, Melissa B.; Shah, Tapan A.; Shaikh, Nadia N.

2016-01-01

The concentration, location, and timing of bone morphogenetic protein 2 (BMP2, HGNC:1069, GeneID: 650) gene expression must be precisely regulated. Abnormal BMP2 levels cause congenital anomalies and diseases involving the mesenchymal cells that differentiate into muscle, fat, cartilage, and bone. The molecules and conditions that influence BMP2 synthesis are diverse. Understandably, complex mechanisms control Bmp2 gene expression. This review includes a compilation of agents and conditions that can induce Bmp2. The currently known trans-regulatory factors and cis-regulatory elements that modulate Bmp2 expression are summarized and discussed. This article is protected by copyright. All rights reserved PMID:25776852

METHOD FOR PRODUCING THORIUM TETRACHLORIDE

DOEpatents

Mason, E.A.; Cobb, C.M.

1960-03-15

A process for producing thorium tetrachloride from thorium concentrate comprises reacting thorium concentrates with a carbonaceous reducing agent in excess of 0.05 part by weight per part of thoriferous concentrate at a temperature in excess of 1300 deg C, cooling and comminuting the mass, chlorinating the resulting comminuting mass by suspending in a gaseous chlorinating agent in a fluidized reactor at a temperatare maintained between about l85 deg C and 770 deg C, and removing the resulting solid ThCl/sub 4/ from the reaction zone.

Research on magnetic separation for complex nickel deep removal and magnetic seed recycling.

PubMed

Qiu, Yiqin; Xiao, Xiao; Ye, Ziwei; Guan, Zhijie; Sun, Shuiyu; Ren, Jie; Yan, Pingfan

2017-04-01

This study investigated the deep removal of complex nickel from simulated wastewater using magnetic separation and magnetic seed recycling. Nano-magnetite (Fe 3 O 4 ) was used as the magnetic seed. The flocculant applied was N,N-bis-(dithiocarboxy) ethanediamine (EDTC), a highly efficient heavy metal chelating agent included in dithiocarbamate (DTC). Important investigated parameters included hydraulic retention time, magnetic seed dosage, and magnetic field strength. The study also explored the magnetic flocculation mechanism involved in the reaction. The result indicated that the residual Ni concentration was reduced to less than 0.1 mg/L from the initial concentration of 50 mg/L under optimal conditions. Magnetic seed recovery reached 76.42% after a 3-h stirring period; recycled magnetic seeds were analyzed using scanning electron microscope (SEM) and X-ray diffraction (XRD). The zeta potential results illustrated that magnetic seeds firmly combined with flocs when the pH ranged from 6.5 to 7.5 due to the electrostatic attraction. When the pH was less than 7, magnetic seeds and EDTC were also combined due to electrostatic attraction. Particle size did affect microfloc size; it decreased microfloc size and increased floc volume through magnetic seed loading. The effective binding sites between flocs and magnetic seeds increased when adding the magnetic seeds. This led the majority of magnetic flocs to be integrated with the magnetic seeds, which served as a nucleus to enhance the flocculation property and ultimately improve the nickel complex removal rate.

Experimental considerations in metal mobilization from soil by chelating ligands: The influence of soil-solution ratio and pre-equilibration - A case study on Fe acquisition by phytosiderophores.

PubMed

Schenkeveld, W D C; Kimber, R L; Walter, M; Oburger, E; Puschenreiter, M; Kraemer, S M

2017-02-01

The efficiency of chelating ligands in mobilizing metals from soils and sediments is generally examined under conditions remote from those under which they are exuded or applied in the field. This may lead to incorrect estimations of the mobilizing efficiency. The aim of this study was to establish the influence of the soil solution ratio (SSR) and pre-equilibration with electrolyte solution on metal mobilization and metal displacement. For this purpose a series of interaction experiments with a calcareous clay soil and a biogenic chelating agent, the phytosiderophore 2'-deoxymugineic acid (DMA) were carried out. For a fixed ligand concentration, the SSR had a strong influence on metal mobilization and displacement. Metal complexation was faster at higher SSR. Reactive pools of metals that were predominantly mobilized at SSR 6 (in this case Cu), became depleted at SSR 0.1, whereas metals that were marginally mobilized at SSR 6, were dominantly mobilized at SSR 0.1 (in this case Fe), because of large soil reactive pools. For a fixed "amount of ligand"-to-"amount of soil"-ratio, metal complexation scaled linearly with the SSR. The efficiency of ligands in mobilizing metals under field conditions can be predicted with batch experiments, as long as the ligand-to-soil-ratio is matched. In most previously reported studies this criterion was not met. Equivalent metal-complex concentrations under field conditions can be back-calculated using adsorption isotherms for the respective metal-complexes. Drying and dry storage created labile pools of Fe, Cu and Zn, which were rapidly mobilized upon addition of DMA solution to dry soil. Pre-equilibration decreased these labile pools, leading to smaller concentrations of these metals during initial mobilization, but did not reduce the lag time between ligand addition and onset of microbial degradation of the metal-complexes. Hence SSR and pre-equilibration should be carefully considered when testing the metal mobilizing efficiency of chelating ligands. Copyright © 2016. Published by Elsevier B.V.

Antimony film sensor for sensitive rare earth metal analysis in environmental samples.

PubMed

Makombe, Martin; van der Horst, Charlton; Silwana, Bongiwe; Iwuoha, Emmanuel; Somerset, Vernon

2016-07-02

A sensor for the adsorptive stripping voltammetric determination of rare earth elements has been developed. The electrochemical procedure is based on the oxidation of the rare earth elements complexed with alizarin complexone at a glassy carbon electrode that was in situ modified with an antimony film, during an anodic scan from -0.2 V to 1.1 V (vs. Ag/AgCl) and deposition potential of -0.1 V (vs. Ag/AgCl). The factors influencing the adsorptive stripping capability were optimised, including the complexing agent concentration, plating concentration of antimony and deposition time. The detection of rare earth elements (La, Ce and Pr) were realised in 0.08 M sodium acetate (pH = 5.8) solution as supporting electrolyte, with 2 × 10(-6) M alizarin complexone and 1.0 mg L(-1) antimony solution. Under the optimised conditions, a deposition time of 360 s was obtained and a linear response was observed between 1 and 25 µg L(-1). The reproducibility of the voltammetric measurements was found to be within 5.0% RSD for 12 replicate measurements of cerium(III) concentration of 5 µg L(-1) using the same electrode surface. The detection limits obtained using stripping analysis was 0.06, 0.42 and 0.71 μg L(-1) for Ce(III), La(III) and Pr(III), respectively. The developed sensor has been successfully applied for the determination of cerium, lanthanum and praseodymium in municipal tap water samples.

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition.

PubMed

Desbois, Nicolas; Pacquelet, Sandrine; Dubois, Adrien; Michelin, Clément; Gros, Claude P

2015-01-01

The Cu(I)-catalysed Huisgen cycloaddition, known as "click" reaction, has been applied to the synthesis of a range of triazole-linked porphyrin/corrole to DOTA/NOTA derivatives. Microwave irradiation significantly accelerates the reaction. The synthesis of heterobimetallic complexes was easily achieved in up to 60% isolated yield. Heterobimetallic complexes were easily prepared as potential MRI/PET (SPECT) bimodal contrast agents incorporating one metal (Mn, Gd) for the enhancement of contrast for MRI applications and one "cold" metal (Cu, Ga, In) for future radionuclear imaging applications. Preliminary relaxivity measurements showed that the reported complexes are promising contrast agents (CA) in MRI.

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

PubMed Central

Desbois, Nicolas; Pacquelet, Sandrine; Dubois, Adrien; Michelin, Clément

2015-01-01

Summary The Cu(I)-catalysed Huisgen cycloaddition, known as “click” reaction, has been applied to the synthesis of a range of triazole-linked porphyrin/corrole to DOTA/NOTA derivatives. Microwave irradiation significantly accelerates the reaction. The synthesis of heterobimetallic complexes was easily achieved in up to 60% isolated yield. Heterobimetallic complexes were easily prepared as potential MRI/PET (SPECT) bimodal contrast agents incorporating one metal (Mn, Gd) for the enhancement of contrast for MRI applications and one “cold” metal (Cu, Ga, In) for future radionuclear imaging applications. Preliminary relaxivity measurements showed that the reported complexes are promising contrast agents (CA) in MRI. PMID:26664643

Particle size and shape modification of hydroxyapatite nanostructures synthesized via a complexing agent-assisted route.

PubMed

Mohandes, Fatemeh; Salavati-Niasari, Masoud

2014-07-01

In this work, hydroxyapatite (HAP), Ca10(PO4)6(OH)2, nanostructures including nanorods, nanobundles and nanoparticles have been prepared via a simple precipitation method. In the present method, Ca(NO3)2·4H2O and (NH4)2HPO4 were used as calcium and phosphorus precursors, respectively. Besides, the Schiff bases derived from 2-hydroxyacetophenone and different diamines were used as complexing agents for the in situ formation of Ca(2+) complexes. The formation mechanism of 0-D and 1-D nanostructures of HAP was also considered. When the complexing agents could coordinate to the Ca(2+) ions through N and O atoms to form the [CaN2O2](2+) complexes, HAP nanoparticles were generated. On the other hand, nanorods and nanobundles of HAP were obtained by forming the [CaN2](2+) as well as [CaO2](2+) complexes in the reaction solution. This work is the first successful synthesis of pure HAP nanostructures in the presence of Schiff bases instead of using the common surfactants. Copyright © 2014 Elsevier B.V. All rights reserved.

Revisiting caffeate's capabilities as a complexation agent to silver cation in mining processes by means of the dual descriptor--a conceptual DFT approach.

PubMed

Martínez-Araya, Jorge Ignacio

2012-09-01

Caffeic acid (C(9)H(8)O(4)) and its conjugate base C(9)H(7)O(4) (-) (anionic form-known as caffeate) were analyzed computationally through the use of quantum chemistry to assess their intrinsic global and local reactivity using the tools of conceptual density functional theory. The anionic form was found to be better at coordinating the silver cation than caffeic acid thus suggesting the use of caffeate as a complexation agent. The complexation capability of caffeate was compared with that of some of the most common ligand agents used to coordinate silver cations. Local reactivity descriptors allowed identification of the preferred sites on caffeate for silver cation coordination thus generating a plausible silver complex. All silver complexes were analyzed thermodynamically considering interaction energies in both gas and aqueous phases; the complexation free energy in aqueous phase was also determined. These results suggest that more attention be paid to the caffeate anion and its derivatives because this work has shed new light on the behavior of this anion in the recovery of silver cations that could be exploited in silver mining processes in a environmentally friendly way.

Electrokinetic treatment of an agricultural soil contaminated with heavy metals.

PubMed

Figueroa, Arylein; Cameselle, Claudio; Gouveia, Susana; Hansen, Henrik K

2016-07-28

The high organic matter content in agricultural soils tends to complex and retain contaminants such as heavy metals. Electrokinetic remediation was tested in an agricultural soil contaminated with Co(+2), Zn(+2), Cd(+2), Cu(+2), Cr(VI), Pb(+2) and Hg(+2). The unenhanced electrokinetic treatment was not able to remove heavy metals from the soil due to the formation of precipitates in the alkaline environment in the soil section close to the cathode. Moreover, the interaction between metals and organic matter probably limited metal transportation under the effect of the electric field. Citric acid and ethylenediaminetetraacetic acid (EDTA) were used in the catholyte as complexing agents in order to enhance the extractability and removal of heavy metals from soil. These complexing agents formed negatively charged complexes that migrated towards the anode. The acid front electrogenerated at the anode favored the dissolution of heavy metals that were transported towards the cathode. The combined effect of the soil pH and the complexing agents resulted in the accumulation of heavy metals in the center of the soil specimen.

The slow cell death response when screening chemotherapeutic agents.

PubMed

Blois, Joseph; Smith, Adam; Josephson, Lee

2011-09-01

To examine the correlation between cell death and a common surrogate of death used in screening assays, we compared cell death responses to those obtained with the sulforhodamine B (SRB) cell protein-based "cytotoxicity" assay. With the SRB assay, the Hill equation was used to obtain an IC50 and final cell mass, or cell mass present at infinite agent concentrations, with eight adherent cell lines and four agents (32 agent/cell combinations). Cells were treated with high agent concentrations (well above the SRB IC50) and the death response determined as the time-dependent decrease in cells failing to bind both annexin V and vital fluorochromes by flow cytometry. Death kinetics were categorized as fast (5/32) (similar to the reference nonadherent Jurkat line), slow (17/32), or none (10/32), despite positive responses in the SRB assay in all cases. With slow cell death, a single exposure to a chemotherapeutic agent caused a slow, progressive increase in dead (necrotic) and dying (apoptotic) cells for at least 72 h. Cell death (defined by annexin and/or fluorochrome binding) did not correlate with the standard SRB "cytotoxicity" assay. With the slow cell death response, a single exposure to an agent caused a slow conversion from vital to apoptotic and necrotic cells over at least 72 h (the longest time point examined). Here, increasing the time of exposure to agent concentrations modestly above the SRB IC50 provides a method of maximizing cell kill. If tumors respond similarly, sustained low doses of chemotherapeutic agents, rather than a log-kill, maximum tolerated dose strategy may be an optimal strategy of maximizing tumor cell death.

Hafnium-Based Contrast Agents for X-ray Computed Tomography.

PubMed

Berger, Markus; Bauser, Marcus; Frenzel, Thomas; Hilger, Christoph Stephan; Jost, Gregor; Lauria, Silvia; Morgenstern, Bernd; Neis, Christian; Pietsch, Hubertus; Sülzle, Detlev; Hegetschweiler, Kaspar

2017-05-15

Heavy-metal-based contrast agents (CAs) offer enhanced X-ray absorption for X-ray computed tomography (CT) compared to the currently used iodinated CAs. We report the discovery of new lanthanide and hafnium azainositol complexes and their optimization with respect to high water solubility and stability. Our efforts culminated in the synthesis of BAY-576, an uncharged hafnium complex with 3:2 stoichiometry and broken complex symmetry. The superior properties of this asymmetrically substituted hafnium CA were demonstrated by a CT angiography study in rabbits that revealed excellent signal contrast enhancement.

On the use of multi-agent systems for the monitoring of industrial systems

NASA Astrophysics Data System (ADS)

Rezki, Nafissa; Kazar, Okba; Mouss, Leila Hayet; Kahloul, Laid; Rezki, Djamil

2016-03-01

The objective of the current paper is to present an intelligent system for complex process monitoring, based on artificial intelligence technologies. This system aims to realize with success all the complex process monitoring tasks that are: detection, diagnosis, identification and reconfiguration. For this purpose, the development of a multi-agent system that combines multiple intelligences such as: multivariate control charts, neural networks, Bayesian networks and expert systems has became a necessity. The proposed system is evaluated in the monitoring of the complex process Tennessee Eastman process.

Evaluation of CO2, N2 and He as Fire Suppression Agents in Microgravity

NASA Technical Reports Server (NTRS)

Ruff, Gary A.; Hicks, Michael; Pettegrew, Richard

2004-01-01

The U.S. modules of the International Space Station use gaseous CO2 as the fire extinguishing agent. This was selected as a result of extensive experience with CO2 as a fire suppressant in terrestrial applications, trade studies on various suppressants, and experiments. The selection of fire suppressants and suppression strategies for NASA s Lunar and Martian exploration missions will be based on the same studies and normal-gravity data unless reduced gravity fire suppression data is obtained. In this study, the suppressant agent concentrations required to extinguish a flame in low velocity convective flows within the 20-sec of low gravity on the KC-135 aircraft were investigated. Suppressant gas mixtures of CO2, N2, and He with the balance being oxygen/nitrogen mixtures with either 21% or 25% O2 were used to suppress flames on a 19-mm diameter PMMA cylinder in reduced gravity. For each of the suppressant mixtures, limiting concentrations were established that would extinguish the flame at any velocity. Similarly, concentrations were established that would not extinguish the flame. The limiting concentrations were generally consistent with previous studies but did suggest that geometry had an effect on the limiting conditions. Between the extinction and non-extinction limits, the suppression characteristics depended on the extinguishing agent, flow velocity, and O2 concentration. The limiting velocity data from the CO2, He, and N2 suppressants were well correlated using an effective mixture enthalpy per mole of O2, indicating that all act via O2 displacement and cooling mechanisms. In reduced gravity, the agent concentration required to suppress the flames increased as the velocity increased, up to approximately 10 cm/s (the maximum velocity evaluated in this experiment). The effective enthalpy required to extinguish flames at velocities of 10 cm/s is approximately the same as the concentrations in normal gravity. A computational study is underway to further evaluate these findings.

Uptake of Plutonium-238 into Solanum tuberosum L. (potato plants) in presence of complexing agent EDTA.

PubMed

Tawussi, Frank; Gupta, Dharmendra K; Mühr-Ebert, Elena L; Schneider, Stephanie; Bister, Stefan; Walther, Clemens

2017-11-01

Bioavailability and plant uptake of radionuclides depend on various factors. Transfer into different plant parts depends on chemical and physical processes, which need to be known for realistic ingestion dose modelling when these plants are used for food. Within the scope of the present work, the plutonium uptake by potato plants (Solanum tuberosum L.) was investigated in hydroponic solution of low concentration [Pu] = 10 -9  mol L -1 . Particular attention was paid to the speciation of radionuclides in the solution which was modelled by the speciation code PHREEQC. The speciation, the solubility and therefore the plant availability of radionuclides mainly depend on the pH value and the redox potential of the solution. During the contamination period, the redox potential did not change significantly. In contrast, the pH value showed characteristic changes depending on exudates excreted by the plants. Plant roots took up high amounts of plutonium (37%-50% of the added total amount). In addition to the uptake into the roots, the radionuclides can also adsorb to the exterior root surface. The solution-to-plant transfer factor showed values between 0.03 and 0.80 (Bq kg -1 / Bq L -1 ) for the potato tubers. By addition of the complexing agent EDTA (10 -4  mol L-1), the plutonium uptake from solution increased by 58% in tubers and by 155% in shoots/leaves. The results showed that excreted substances by plants affect bioavailability of radionuclides at low concentration, on the one hand. On the other hand, the uptake of plutonium by roots and the accumulation in different plant parts can lead to non-negligible ingestion doses, even at low concentration. We are aware of the limited transferability of data obtained in hydroponic solutions to plants growing in soil. However, the aim of this study is twofold: First we want to investigate the influence of Pu speciation on plant uptake in a rather well defined system which can be modelled using available thermodynamic data. Second, techniques developed here shall be applied to the investigation of plants growing in soil in the future. The present work contributes to the basic understanding how plant induced effects on nutrient solution influence bioavailability of radionuclides and fosters the need for more detailed investigations of the complex uptake and accumulation processes of radionuclides into plants. Copyright © 2017 Elsevier Ltd. All rights reserved.

1.13 – Emerging contaminants

USGS Publications Warehouse

Barber, Larry B.

2014-01-01

Since the Industrial Revolution, a diversity of large-scale chemical innovations has impacted aquatic systems in urban environments. Beginning in the 1990s, there has been a growing scientific interest and public awareness of the effects of the chemicals used in domestic, commercial, industrial, and agricultural applications, referred to in this article as ‘emerging contaminants’ (ECs), on ecosystem and human health. The growing global population and its increasing demands on water supplies in conjunction with climate-induced changes in hydrologic regimes place stress on freshwater resources, resulting in a greater reliance on reuse of reclaimed municipal wastewater treatment plant (WWTP) effluents to meet human and environmental needs. WWTP effluents are a major source of ECs, and it is important to have an understanding of the chemical composition of the reclaimed water, because many ECs are biologically active and the effects of chronic exposure to low concentration complex mixtures are unknown. Several classes of ECs that have been shown to be widespread in the aquatic environment are discussed in this chapter, including surfactants, complexing agents, fragrances, antimicrobials, industrial chemicals, pharmaceuticals, natural and synthetic estrogens, and disinfection byproducts. All of these compounds are biologically active via a variety of modes of action, and can occur in aquatic systems at concentrations ranging from <0.001 to >100 μg l−1.

Aquatic Toxicity Screening of Fire Fighting Agents; 2003 Report

DTIC Science & Technology

2003-06-02

Aqueous Film Forming Foam ( AFFF ), the reference toxicant. The aquatic toxicity screening consisted of an acute, static, range-finding...five concentrations of 3M Light Water Brand Aqueous Film Forming Foam ( AFFF ), the reference toxicant. The aquatic toxicity screening consisted of an...experimental foam concentrates against current Military Specification MIL-F-24385F Fire Extinguishing Agent, Aqueous Film Forming Foam

Effects of solution concentration and capping agents on the properties of potassium titanyl phosphate noparticles synthesized using a co-precipitation method

NASA Astrophysics Data System (ADS)

Gharibshahian, E.; Jafar Tafershi, M.; Fazli, M.

2018-05-01

In this study, KTiOPO4 (KTP) nanoparticles were synthesized using a co-precipitation method. The effects of the solution concentration (M) and capping agents, such as PVA, oxalic acid, glycine, triethanolamine, and L-alanine, on the structural, microstructural, and optical properties of the products were investigated using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible spectroscopy, field emission scanning electron microscopy, and transmission electron microscopy. Decreasing the solution concentration decreased the crystallite size from 53.07 nm (for M = 2) to 39.42 nm (for M = 0.5). After applying different capping agents to the sample at the optimum concentration (M = 0.5), the crystallite size decreased again and grains as small as 10.61 nm were obtained. XRD and FTIR analyses indicated the formation of KTP nanoparticles with an orthorhombic structure in all of the samples. The optical band gap increased as the crystallite size decreased. Different morphological patterns such as spherical, needle shaped, polyhedron, and tablet forms were observed in the nanoparticles, which were correlated with the effects of the capping agents employed.

Design, synthesis and evaluation of a new Mn - Contrast agent for MR imaging of myocardium based on the DTPA-phenylpentadecanoic acid complex

NASA Astrophysics Data System (ADS)

Belyanin, Maxim L.; Stepanova, Elena V.; Valiev, Rashid R.; Filimonov, Victor D.; Usov, Vladimir Y.; Borodin, Oleg Y.; Ågren, Hans

2016-11-01

In the present paper we describe the first synthesis and evaluation of a novel Mn (II) complex (DTPA-PPDA Mn (II)) which contains a C-15 fatty acid moiety that has high affinity to the heart muscle. The complexation energy of DTPA-PPDA Mn (II) evaluated by quantum chemistry methodology indicates that it essentially exceeds the corresponding value for the known DTPA Mn (II) complex. Molecular docking revealed that the affinity of the designed complex to the heart-type transport protein H-FABP well exceeds that of lauric acid. Phantom experiments in low-field MRI the designed contrast agent provides MR imaging comparable to gadopentetic acid.

The assessment of electrophysiological activity in human-induced pluripotent stem cell-derived cardiomyocytes exposed to dimethyl sulfoxide and ethanol by manual patch clamp and multi-electrode array system.

PubMed

Hyun, Soo-Wang; Kim, Bo-Ram; Hyun, Sung-Ae; Seo, Joung-Wook

2017-09-01

Recently, electrophysiological activity has been effectively measured in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to predict drug-induced arrhythmia. Dimethyl sulfoxide (DMSO) and ethanol have been used as diluting agents in many experiments. However, the maximum DMSO and ethanol concentrations that can be effectively used in the measurement of electrophysiological parameters in hiPSC-CMs-based patch clamp and multi-electrode array (MEA) have not been fully elucidated. We investigated the effects of varying concentrations of DMSO and ethanol used as diluting agents on several electrophysiological parameters in hiPSC-CMs using patch clamp and MEA. Both DMSO and ethanol at concentrations>1% in external solution resulted in osmolality >400mOsmol/kg, but pH was not affected by either agent. Neither DMSO nor ethanol led to cell death at the concentrations examined. However, resting membrane potential, action potential amplitude, action potential duration at 90% and 40%, and corrected field potential duration were decreased significantly at 1% ethanol concentration. DMSO at 1% also significantly decreased the sodium spike amplitude. In addition, the waveform of action potential and field potential was recorded as irregular at 3% concentrations of both DMSO and ethanol. Concentrations of up to 0.3% of either agent did not affect osmolality, pH, cell death, or electrophysiological parameters in hiPSC-CMs. Our findings suggest that 0.3% is the maximum concentration at which DMSO or ethanol should be used for dilution purposes in hiPSC-CMs-based patch clamp and MEA. Copyright © 2017 Elsevier Inc. All rights reserved.

Performance of an electrochemical carbon monoxide monitor in the presence of anesthetic gases.

PubMed

Dunning, M; Woehlck, H J

1997-11-01

The passage of volatile anesthetic agents through accidentally dried CO2 absorbents in anesthesia circuits can result in the chemical breakdown of anesthetics with production of greater than 10000 ppm carbon monoxide (CO). This study was designed to evaluate a portable CO monitor in the presence of volatile anesthetic agents. Two portable CO monitors employing electrochemical sensors were tested to determine the effects of anesthetic agents, gas sample flow rates, and high CO concentrations on their electrochemical sensor. The portable CO monitors were exposed to gas mixtures of 0 to 500 ppm CO in either 70% nitrous oxide, 1 MAC concentrations of contemporary volatile anesthetics, or reacted isoflurane or desflurane (containing CO and CHF3) in oxygen. The CO measurements from the electrochemical sensors were compared to simultaneously obtained samples measured by gas chromatography (GC). Data were analyzed by linear regression. Overall correlation between the portable CO monitors and the GC resulted in an r2 value >0.98 for all anesthetic agents. Sequestered samples produced an exponential decay of measured CO with time, whereas stable measurements were maintained during continuous flow across the sensor. Increasing flow rates resulted in higher CO readings. Exposing the CO sensor to 3000 and 19000 ppm CO resulted in maximum reported concentrations of approximately 1250 ppm, with a prolonged recovery. Decrease in measured concentration of the sequestered samples suggests destruction of the sample by the sensor, whereas a diffusion limitation is suggested by the dependency of measured value upon flow. Any value over 500 ppm must be assumed to represent dangerous concentrations of CO because of the non-linear response of these monitors at very high CO concentrations. These portable electrochemical CO monitors are adequate to measure CO concentrations up to 500 ppm in the presence of typical clinical concentrations of anesthetics.

The safety of antituberculosis medications during breastfeeding.

PubMed

Tran, J H; Montakantikul, P

1998-12-01

Most antituberculosis drugs appear to be safe for use with breastfeeding. These agents are excreted in breast milk at relatively small concentrations. No adverse effects have been reported to date. The percentages of the therapeutic dose of antituberculosis agents that potentially may be delivered to the nursing infants range from 0.05% to 28%. Currently isoniazid, rifampin, ethambutol, streptomycin (first-line agents), kanamycin and cycloserine (second-line agents) are the only agents considered by the AAP to be compatible with breastfeeding. Unfortunately, there are still no clear data on the safety of pyrazinamide, ethionamide, and capreomycin during breastfeeding. If the mother chooses to breastfeed, it may be prudent to examine the infant for signs and symptoms of toxicity. In infants requiring treatment with antituberculosis agents, it is important to use therapeutic doses since drug concentrations in breast milk are not adequate as effective therapy for treatment or prevention. However, dosing at the lower end of the therapeutic range should be prescribed (i.e., 10 mg/kg/day of isoniazid) to decrease the risk of toxicity.

Influence of dispersing agents and solution conditions on the solubility of crude kaolin.

PubMed

Zaman, Abbas A; Mathur, Sharad

2004-03-01

Experiments measuring the solubility of kaolin particles in terms of the concentration of aluminum and silicon ions in supernatant were carried out as a function of the pH of the slurry over a wide range of dosages of different dispersing agents varying from 0.5 to 12 mg/(g solids). The concentrations of the metal ions in supernatant were found to be strongly affected by the type and the dosage of the dispersants and pH of the solution. In this study, the mechanism of the reaction between the dispersing agents and kaolin particles was studied and the dissolution capacities of metal ions (aluminum and silicon) were identified from kaolin particles in the absence and presence of dispersing agents. The three anionic dispersing agents used were sodium polyacrylate (Na-PAA), sodium hexametaphosphate (Na-HMP), and sodium silicate (Na-silicate), based on the industrial application of these agents and their ability to produce a stable dispersion for this purpose.

Effect of Two Cancer Chemotherapeutic Agents on the Antibacterial Activity of Three Antimicrobial Agents

PubMed Central

Moody, Marcia R.; Morris, Maureen J.; Young, Viola Mae; Moyé, Lemuel A.; Schimpff, Stephen C.; Wiernik, Peter H.

1978-01-01

Cancer chemotherapeutic agents and antibacterial antibiotics are often given concomitantly. Daunorubicin, cytosine arabinoside, and three antibiotics (gentamicin, amikacin, and ticarcillin) were tested individually and in combinations to determine their antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. These cytotoxic agents are commonly employed in the therapy of acute nonlymphocytic leukemia for remission induction therapy, and these antimicrobial agents are used in infection therapy. The maximum concentrations of the two cytotoxic drugs were chosen to be twice the known peak plasma levels of commonly employed dosage schedules. Neither of the cancer chemotherapeutic agents, alone or in combination, demonstrated bactericidal activity at the levels tested. However, in the presence of these agents, the antimicrobial activity of gentamicin and amikacin, although not that of ticarcillin, was depressed for 11 of 15 K. pneumoniae strains and 8 of 15 P. aeruginosa strains, but for none of the strains of E. coli. This level of decreased activity occasionally resulted in a minimal inhibitory concentration of the tested aminoglycoside well above the standard serum levels. Daunorubicin was more likely to antagonize gentamicin than was cytosine arabinoside. PMID:103494