Sample records for agents design synthesis

  1. Intelligent Agents and Their Potential for Future Design and Synthesis Environment

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K. (Compiler); Malone, John B. (Compiler)

    1999-01-01

    This document contains the proceedings of the Workshop on Intelligent Agents and Their Potential for Future Design and Synthesis Environment, held at NASA Langley Research Center, Hampton, VA, September 16-17, 1998. The workshop was jointly sponsored by the University of Virginia's Center for Advanced Computational Technology and NASA. Workshop attendees came from NASA, industry and universities. The objectives of the workshop were to assess the status of intelligent agents technology and to identify the potential of software agents for use in future design and synthesis environment. The presentations covered the current status of agent technology and several applications of intelligent software agents. Certain materials and products are identified in this publication in order to specify adequately the materials and products that were investigated in the research effort. In no case does such identification imply recommendation or endorsement of products by NASA, nor does it imply that the materials and products are the only ones or the best ones available for this purpose. In many cases equivalent materials and products are available and would probably produce equivalent results.

  2. Intelligent Agents for Design and Synthesis Environments: My Summary

    NASA Technical Reports Server (NTRS)

    Norvig, Peter

    1999-01-01

    This presentation gives a summary of intelligent agents for design synthesis environments. We'll start with the conclusions, and work backwards to justify them. First, an important assumption is that agents (whatever they are) are good for software engineering. This is especially true for software that operates in an uncertain, changing environment. The "real world" of physical artifacts is like that: uncertain in what we can measure, changing in that things are always breaking down, and we must interact with non-software entities. The second point is that software engineering techniques can contribute to good design. There may have been a time when we wanted to build simple artifacts containing little or no software. But modern aircraft and spacecraft are complex, and rely on a great deal of software. So better software engineering leads to better designed artifacts, especially when we are designing a series of related artifacts and can amortize the costs of software development. The third point is that agents are especially useful for design tasks, above and beyond their general usefulness for software engineering, and the usefulness of software engineering to design.

  3. Intelligent microchip networks: an agent-on-chip synthesis framework for the design of smart and robust sensor networks

    NASA Astrophysics Data System (ADS)

    Bosse, Stefan

    2013-05-01

    Sensorial materials consisting of high-density, miniaturized, and embedded sensor networks require new robust and reliable data processing and communication approaches. Structural health monitoring is one major field of application for sensorial materials. Each sensor node provides some kind of sensor, electronics, data processing, and communication with a strong focus on microchip-level implementation to meet the goals of miniaturization and low-power energy environments, a prerequisite for autonomous behaviour and operation. Reliability requires robustness of the entire system in the presence of node, link, data processing, and communication failures. Interaction between nodes is required to manage and distribute information. One common interaction model is the mobile agent. An agent approach provides stronger autonomy than a traditional object or remote-procedure-call based approach. Agents can decide for themselves, which actions are performed, and they are capable of flexible behaviour, reacting on the environment and other agents, providing some degree of robustness. Traditionally multi-agent systems are abstract programming models which are implemented in software and executed on program controlled computer architectures. This approach does not well scale to micro-chip level and requires full equipped computers and communication structures, and the hardware architecture does not consider and reflect the requirements for agent processing and interaction. We propose and demonstrate a novel design paradigm for reliable distributed data processing systems and a synthesis methodology and framework for multi-agent systems implementable entirely on microchip-level with resource and power constrained digital logic supporting Agent-On-Chip architectures (AoC). The agent behaviour and mobility is fully integrated on the micro-chip using pipelined communicating processes implemented with finite-state machines and register-transfer logic. The agent behaviour

  4. Synthesis of Purine Nucleoside and Nucleotide Analogs as Antiparasitic Agents.

    DTIC Science & Technology

    1979-09-01

    was to conduct studies on the synthesis of purine nucleoside and nucleotide analogs as anti- parasitic agents. The primary target compounds were 5...antiparasitic agents. - Jaffe has proposed that the susceptibility of pathogenic helminths and protozoa to fraudulent purine, in contrast to pyrimidine...8217-substituted derivatives are thus designed to inhibit nucleoside and nucleotide kinases as well as other parasitic enzymes. Mammalian cells, onthe

  5. Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents

    PubMed Central

    Fedorova, Elena V.; Buryakina, Anna V.; Zakharov, Alexey V.; Filimonov, Dmitry A.; Lagunin, Alexey A.; Poroikov, Vladimir V.

    2014-01-01

    Based on the data about structure and antidiabetic activity of twenty seven vanadium and zinc coordination complexes collected from literature we developed QSAR models using the GUSAR program. These QSAR models were applied to 10 novel vanadium coordination complexes designed in silico in order to predict their hypoglycemic action. The five most promising substances with predicted potent hypoglycemic action were selected for chemical synthesis and pharmacological evaluation. The selected coordination vanadium complexes were synthesized and tested in vitro and in vivo for their hypoglycemic activities and acute rat toxicity. Estimation of acute rat toxicity of these five vanadium complexes was performed using a freely available web-resource (http://way2drug.com/GUSAR/acutoxpredict.html). It has shown that the selected compounds belong to the class of moderate toxic pharmaceutical agents, according to the scale of Hodge and Sterner. Comparison with the predicted data has demonstrated a reasonable correspondence between the experimental and predicted values of hypoglycemic activity and toxicity. Bis{tert-butyl[amino(imino)methyl]carbamato}oxovanadium (IV) and sodium(2,2′-Bipyridyl)oxo-diperoxovanadate(V) octahydrate were identified as the most potent hypoglycemic agents among the synthesized compounds. PMID:25057899

  6. One-pot synthesis of MWW zeolite nanosheets using a rationally designed organic structure-directing agent

    DOE PAGES

    Luo, Helen Y.; Michaelis, Vladimir K.; Hodges, Sydney; ...

    2015-07-22

    A new material MIT-1 comprised of delaminated MWW zeolite nanosheets is synthesized in one-pot using a rationally designed organic structure-directing agent (OSDA). The OSDA is comprised of a hydrophilic head segment that resembles the OSDA used to synthesize the zeolite precursor MCM22(P), a hydrophobic tail segment that resembles the swelling agent used to swell MCM22(P), and a di-quaternary ammonium linker that connects both segments. MIT-1 features high crystallinity and surface areas exceeding 500 m 2g -1, and can be synthesized over a wide synthesis window that includes Si/Al ratios ranging from 13 to 67. Characterization data reveal high mesoporosity andmore » acid strength with no detectable amorphous silica phases. In conclusion, compared to MCM-22 and MCM-56, MIT-1 shows a three-fold increase in catalytic activity for the Friedel-Crafts alkylation of benzene with benzyl alcohol.« less

  7. Design and Synthesis of Curcumin-Like Diarylpentanoid Analogues as Potential Anticancer Agents.

    PubMed

    Qudjani, Elahe; Iman, Maryam; Davood, Asghar; Ramandi, Mahdi F; Shafiee, Abbas

    2016-01-01

    Curcumin is a polyphenolic natural compound with multiple targets that used for the prophylaxis and treatment of some type of cancers like cervical and pancreatic cancers. Some recent patent for curcumin for cancer has also been reviewed. In this study, ten new curcumin derivatives were designed and synthesized and their cytostatic activity evaluated against the Hela and Panc cell lines that some of them showed more activity than curcumin. In the present study, a series of mono-carbonyl derivatives of curcumin were designed and prepared. The details of the synthesis and chemical characterization of the synthesized compounds are described. The cytostatic activities of the designed compounds are assessed in two different tumor cell lines using MTT test. In vitro screening for human cervix carcinoma cell lines (Hela) and pancreatic cell lines (Panc-1) at 24 and 48 hour showed that all the analogs possessed good activity against these tumor cell lines and compounds 5a, 5c and 6 with high potency can be used as a new lead compounds for the designing and finding new and potent cytostatic agents. Docking studies indicated that compound 5c readily binds the active site of human glyoxalase I protein via two strong hydrogen bonds engaging residues of Glu-99 and Lys-156. Our results are useful in guiding a design of optimized ligands with improved pharmacokinetic properties and increased of anti-cancer activity vs. the prototype curcumin compound.

  8. Enantioselective Total Synthesis of Antibiotic CJ-16,264, Synthesis and Biological Evaluation of Designed Analogues, and Discovery of Highly Potent and Simpler Antibacterial Agents.

    PubMed

    Nicolaou, K C; Pulukuri, Kiran Kumar; Rigol, Stephan; Buchman, Marek; Shah, Akshay A; Cen, Nicholas; McCurry, Megan D; Beabout, Kathryn; Shamoo, Yousif

    2017-11-08

    An improved and enantioselective total synthesis of antibiotic CJ-16,264 through a practical kinetic resolution and an iodolactonization reaction to form the iodo pyrrolizidinone fragment of the molecule is described. A series of racemic and enantiopure analogues of CJ-16,264 was designed and synthesized through the developed synthetic technologies and tested against drug-resistant bacterial strains. These studies led to interesting structure-activity relationships and the identification of a number of simpler, and yet equipotent, or even more potent, antibacterial agents than the natural product, thereby setting the foundation for further investigations in the quest for new anti-infective drugs.

  9. Single Agents with Designed Combination Chemotherapy Potential: Synthesis and Evaluation of Substituted Pyrimido[4,5-b]indoles as Receptor Tyrosine Kinase and Thymidylate Synthase Inhibitors and as Antitumor Agents

    PubMed Central

    Gangjee, Aleem; Zaware, Nilesh; Raghavan, Sudhir; Ihnat, Michael; Shenoy, Satyendra; Kisliuk, Roy L.

    2010-01-01

    Combinations of antiangiogenic agents (AAs) with cytotoxic agents have shown significant promise and several such clinical trials are currently underway. We have designed, synthesized and evaluated two compounds that each inhibit vascular endothelial growth factor receptor-2 (VEGFR-2) and platelet derived growth factor receptor-beta (PDGFR-β) for antiangiogenic effects and also inhibit human thymidylate synthase (hTS) for cytotoxic effects in single agents. The synthesis of these compounds involved the nucleophilic displacement of the common intermediate 5-chloro-9H-pyrimido[4,5-b]indole-2,4-diamine with appropriate benzenethiols. The inhibitory potency of both these single agents against VEGFR-2, PDGFR-β and hTS is better than or close to standards. In a COLO-205 xenograft mouse model one of the analogs significantly decreased tumor growth (TGI = 76% at 35 mg/kg), liver metastases and tumor blood vessels compared to a standard drug and to control and thus demonstrated potent tumor growth inhibition, inhibition of metastasis and antiangiogenic effects in vivo. These compounds afford combination chemotherapeutic potential in single agents. PMID:20092323

  10. Design, synthesis and biological evaluation of arylcinnamide hybrid derivatives as novel anticancer agents

    PubMed Central

    Romagnoli, Romeo; Baraldi, Pier Giovanni; Salvador, Maria Kimatrai; Chayah, Mariem; Camacho, M. Encarnacion; Prencipe, Filippo; Hamel, Ernest; Consolaro, Francesca; Basso, Giuseppe; Viola, Giampietro

    2014-01-01

    The combination of two pharmacophores into a single molecule represents one of the methods that can be adopted for the synthesis of new anticancer molecules. A series of novel antiproliferative agents designed by a pharmacophore hybridization approach, combining the arylcinnamide skeleton and an α-bromoacryloyl moiety, was synthesized and evaluated for its antiproliferative activity against a panel of seven human cancer cell lines. In addition, the new derivatives were also active on multidrug-resistant cell lines over-expressing P-glycoprotein. The biological effects of various substituents on the N-phenyl ring of the benzamide portion were also described. In order to study the possible mechanism of action, we observed that 4p slightly increased the Reactive Oxygen Species (ROS) production in HeLa cells, but, more importantly, a remarkable decrease of intracellular reduced glutathione content was detected in treated cells compared with controls. These results were confirmed by the observation that only thiol-containing antioxidants were able to significantly protect the cells from induced cell death. Altogether our results indicate that the new derivatives are endowed with good anticancer activity in vitro, and their properties may result in the development of new cancer therapeutic strategies. PMID:24858544

  11. Anti-AIDS agents 81. Design, synthesis, and structure-activity relationship study of betulinic acid and moronic acid derivatives as potent HIV maturation inhibitors.

    PubMed

    Qian, Keduo; Kuo, Reen-Yun; Chen, Chin-Ho; Huang, Li; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2010-04-22

    In our continuing study of triterpene derivatives as potent anti-HIV agents, different C-3 conformationally restricted betulinic acid (BA, 1) derivatives were designed and synthesized in order to explore the conformational space of the C-3 pharmacophore. 3-O-Monomethylsuccinyl-betulinic acid (MSB) analogues were also designed to better understand the contribution of the C-3' dimethyl group of bevirimat (2), the first-in-class HIV maturation inhibitor, which is currently in phase IIb clinical trials. In addition, another triterpene skeleton, moronic acid (MA, 3), was also employed to study the influence of the backbone and the C-3 modification toward the anti-HIV activity of this compound class. This study enabled us to better understand the structure-activity relationships (SAR) of triterpene-derived anti-HIV agents and led to the design and synthesis of compound 12 (EC(50): 0.0006 microM), which displayed slightly better activity than 2 as a HIV-1 maturation inhibitor.

  12. 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.

  13. Synthesis of (+)-Antroquinonol: An Antihyperglycemic Agent.

    PubMed

    Sulake, Rohidas S; Lin, Hsiao-Han; Hsu, Chia-Yu; Weng, Ching-Feng; Chen, Chinpiao

    2015-06-19

    The total synthesis of antroquinonol has been accomplished through Suzuki-Miyaura cross-coupling and Barton-McCombie reaction, and the α,β-unsaturation was achieved through selenylation and oxidation protocols. In vitro and in vivo studies on the glucose-lowering properties of antroquinonol indicate that it is a potential antidiabetic agent.

  14. Capping agents in nanoparticle synthesis: Surfactant and solvent system

    NASA Astrophysics Data System (ADS)

    Gulati, Shivani; Sachdeva, M.; Bhasin, K. K.

    2018-05-01

    The preparation of nanomaterials by organometallic precursors require a capping agent, which primarily acts as stabilizing agent and provide colloidal stability along with preventing agglomeration and stopping uncontrolled growth. Final morphology of nanocrystal largely depends on the type of capping agent which is adsorbed on the surface of nanocrystal. Thus capping agents are the keys to obtain the small-sized nanoparticles and are very frequently used in colloidal synthesis of nanoparticles to avoid its overgrowth.

  15. One-pot synthesis of water soluble iron nanoparticles using rationally-designed peptides and ligand release.

    PubMed

    Papst, Stefanie; Cheong, Soshan; Banholzer, Moritz J; Brimble, Margaret A; Williams, David E; Tilley, Richard D

    2013-05-18

    Herein we report the rational design of new phosphopeptides for control of nucleation, growth and aggregation of water-soluble, superparamagnetic iron-iron oxide core-shell nanoparticles. The use of the designed peptides enables a one-pot synthesis that avoids utilizing unstable or toxic iron precursors, organic solvents, and the need for exchange of capping agent after synthesis of the NPs.

  16. Synthesis of mutual azo prodrugs of anti-inflammatory agents and peptides facilitated by α-aminoisobutyric acid.

    PubMed

    Kennedy, David A; Vembu, Nagarajan; Fronczek, Frank R; Devocelle, Marc

    2011-12-02

    Reported is the synthesis of azo mutual prodrugs of the nonsteroidal anti-inflammatory agents (NSAIDs) 4-aminophenylacetic acid (4-APAA) or 5-aminosalicylic acid (5-ASA) with peptides, including an antibiotic peptide temporin analogue modified at the amino terminal by an α-aminoisobutyric acid (Aib) residue. These prodrugs are designed for colonic delivery of two agents to treat infection and inflammation by the bacterial pathogen Clostridium difficile . © 2011 American Chemical Society

  17. Synthesis and Performance of a Biomimetic Indicator for Alkylating Agents.

    PubMed

    Provencher, Philip A; Love, Jennifer A

    2015-10-02

    4-(4-Nitrobenzyl)pyridine (NBP) is a colorimetric indicator compound for many types of carcinogenic alkylating agents. Because of the similar reactivity of NBP and guanine in DNA, NBP serves as a DNA model. NBP assays are used in the toxicological screening of pharmaceutical compounds, detection of chemical warfare agents, environmental hygiene technology, preliminary toxicology tests, mutagenicity of medicinal compounds, and other chemical analyses. Nevertheless, the use of NBP as a DNA model suffers from the compound's low water solubility, its lack of reactive oxygen sites, and dissimilar steric encumbrance compared to DNA. We report herein the design and synthesis of NBP derivatives that address some of these issues. These derivatives have been tested in solution and found to be superior in the colorimetric assay of the alkylating anticancer drug cyclophosphamide. The derivatives have also been integrated into a polymeric silica material which changes color upon the exposure to dangerous alkylating agents, such as iodomethane vapor, without the need for an exogenous base. This material modernizes the NBP assay from a time-consuming laboratory analysis to a real-time solid state sensor, which requires neither solvent nor additional reagents and can detect both gas- and solution-phase alkylating agents.

  18. Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging

    NASA Astrophysics Data System (ADS)

    Shan, Liang; Gu, Xinbin; Wang, Paul

    2013-09-01

    Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, ), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

  19. Streamlined Total Synthesis of Trioxacarcins and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues Thereof. Discovery of Simpler Designed and Potent Trioxacarcin Analogues.

    PubMed

    Nicolaou, K C; Chen, Pengxi; Zhu, Shugao; Cai, Quan; Erande, Rohan D; Li, Ruofan; Sun, Hongbao; Pulukuri, Kiran Kumar; Rigol, Stephan; Aujay, Monette; Sandoval, Joseph; Gavrilyuk, Julia

    2017-11-01

    A streamlined total synthesis of the naturally occurring antitumor agents trioxacarcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including a drug-resistant line. A novel one-step synthesis of anthraquinones and chloro anthraquinones from simple ketone precursors and phenylselenyl chloride is also described. The reported work, featuring novel chemistry and cascade reactions, has potential applications in cancer therapy, including targeted approaches as in antibody-drug conjugates.

  20. 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.

  1. Activation of aluminum as an effective reducing agent by pitting corrosion for wet-chemical synthesis.

    PubMed

    Li, Wei; Cochell, Thomas; Manthiram, Arumugam

    2013-01-01

    Metallic aluminum (Al) is of interest as a reducing agent because of its low standard reduction potential. However, its surface is invariably covered with a dense aluminum oxide film, which prevents its effective use as a reducing agent in wet-chemical synthesis. Pitting corrosion, known as an undesired reaction destroying Al and is enhanced by anions such as F⁻, Cl⁻, and Br⁻ in aqueous solutions, is applied here for the first time to activate Al as a reducing agent for wet-chemical synthesis of a diverse array of metals and alloys. Specifically, we demonstrate the synthesis of highly dispersed palladium nanoparticles on carbon black with stabilizers and the intermetallic Cu₂Sb/C, which are promising candidates, respectively, for fuel cell catalysts and lithium-ion battery anodes. Atomic hydrogen, an intermediate during the pitting corrosion of Al in protonic solvents (e.g., water and ethylene glycol), is validated as the actual reducing agent.

  2. Emergent Aerospace Designs Using Negotiating Autonomous Agents

    NASA Technical Reports Server (NTRS)

    Deshmukh, Abhijit; Middelkoop, Timothy; Krothapalli, Anjaneyulu; Smith, Charles

    2000-01-01

    This paper presents a distributed design methodology where designs emerge as a result of the negotiations between different stake holders in the process, such as cost, performance, reliability, etc. The proposed methodology uses autonomous agents to represent design decision makers. Each agent influences specific design parameters in order to maximize their utility. Since the design parameters depend on the aggregate demand of all the agents in the system, design agents need to negotiate with others in the market economy in order to reach an acceptable utility value. This paper addresses several interesting research issues related to distributed design architectures. First, we present a flexible framework which facilitates decomposition of the design problem. Second, we present overview of a market mechanism for generating acceptable design configurations. Finally, we integrate learning mechanisms in the design process to reduce the computational overhead.

  3. Strategies for the synthesis of the novel antitumor agent peloruside A

    PubMed Central

    Williams, David R; Nag, Partha P; Zorn, Nicolas

    2009-01-01

    The microtubule-stabilizing agent (+)-peloruside A has emerged as a potential therapeutic agent for the treatment of cancer. Two total syntheses have been published and these reports have stimulated additional studies to advance the methodology and strategies for accessing this molecular architecture. This review details the biological data, modeling and conformation analyses, and synthetic studies toward the synthesis of (+)-peloruside A, that were reported prior to December 2007. PMID:18283613

  4. Uncovering the design rules for peptide synthesis of metal nanoparticles.

    PubMed

    Tan, Yen Nee; Lee, Jim Yang; Wang, Daniel I C

    2010-04-28

    Peptides are multifunctional reagents (reducing and capping agents) that can be used for the synthesis of biocompatible metal nanoparticles under relatively mild conditions. However, the progress in peptide synthesis of metal nanoparticles has been slow due to the lack of peptide design rules. It is difficult to establish sequence-reactivity relationships from peptides isolated from biological sources (e.g., biomineralizing organisms) or selected by combinatorial display libraries because of their widely varying compositions and structures. The abundance of random and inactive amino acid sequences in the peptides also increases the difficulty in knowledge extraction. In this study, a "bottom-up" approach was used to formulate a set of rudimentary rules for the size- and shape-controlled peptide synthesis of gold nanoparticles from the properties of the 20 natural alpha-amino acids for AuCl(4)(-) reduction and binding to Au(0). It was discovered that the reduction capability of a peptide depends on the presence of certain reducing amino acid residues, whose activity may be regulated by neighboring residues with different Au(0) binding strengths. Another finding is the effect of peptide net charge on the nucleation and growth of the Au nanoparticles. On the basis of these understandings, several multifunctional peptides were designed to synthesize gold nanoparticles in different morphologies (nanospheres and nanoplates) and with sizes tunable by the strategic placement of selected amino acid residues in the peptide sequence. The methodology presented here and the findings are useful for establishing the scientific basis for the rational design of peptides for the synthesis of metal nanostructures.

  5. 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

  6. 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.

  7. Synthesis and biological activity of imidazopyridine anticoccidial agents: Part II.

    PubMed

    Scribner, Andrew; Dennis, Richard; Lee, Shuliang; Ouvry, Gilles; Perrey, David; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

    2008-06-01

    Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Recently, we reported the synthesis and biological activity of potent imidazo[1,2-a]pyridine anticoccidial agents. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we report the synthesis and anticoccidial activity of a second set of such compounds, focusing on derivatization of the amine side chain at the imidazopyridine 7-position. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

  8. Synthesis and DNA cleavage activity of Bis-3-chloropiperidines as alkylating agents.

    PubMed

    Zuravka, Ivonne; Roesmann, Rolf; Sosic, Alice; Wende, Wolfgang; Pingoud, Alfred; Gatto, Barbara; Göttlich, Richard

    2014-09-01

    Nitrogen mustards are an important class of bifunctional alkylating agents routinely used in chemotherapy. They react with DNA as electrophiles through the formation of highly reactive aziridinium ion intermediates. The antibiotic 593A, with potential antitumor activity, can be considered a naturally occurring piperidine mustard containing a unique 3-chloropiperidine ring. However, the total synthesis of this antibiotic proved to be rather challenging. With the aim of designing simplified analogues of this natural product, we developed an efficient bidirectional synthetic route to bis-3-chloropiperidines joined by flexible, conformationally restricted, or rigid diamine linkers. The key step involves an iodide-catalyzed double cyclization of unsaturated bis-N-chloroamines to simultaneously generate both piperidine rings. Herein we describe the synthesis and subsequent evaluation of a series of novel nitrogen-bridged bis-3-chloropiperidines, enabling the study of the impact of the linker structure on DNA alkylation properties. Our studies reveal that the synthesized compounds possess DNA alkylating abilities and induce strand cleavage, with a strong preference for guanine residues. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Computerized Design Synthesis (CDS), A database-driven multidisciplinary design tool

    NASA Technical Reports Server (NTRS)

    Anderson, D. M.; Bolukbasi, A. O.

    1989-01-01

    The Computerized Design Synthesis (CDS) system under development at McDonnell Douglas Helicopter Company (MDHC) is targeted to make revolutionary improvements in both response time and resource efficiency in the conceptual and preliminary design of rotorcraft systems. It makes the accumulated design database and supporting technology analysis results readily available to designers and analysts of technology, systems, and production, and makes powerful design synthesis software available in a user friendly format.

  10. Design, synthesis and biological evaluation of piperazinyl-β-carbolinederivatives as anti-leishmanial agents.

    PubMed

    Ashok, Penta; Chander, Subhash; Smith, Terry K; Sankaranarayanan, Murugesan

    2018-04-25

    Molecular hybridization is a ligand based drug design approach is well known recent medicinal chemistry to design anti-parasitic agents. In the present study, we have designed a series of (1-phenyl-9H-pyrido [3,4-b]indol-3-yl) (4-phenylpiperazin-1-yl)methanone derivatives using molecular hybridization approach. Designed analogues were evaluated for cytotoxicity and inhibition activity against Leishmania infantum and Leishmania donovani. Among these reported analogues 7b, 7d, 7e, 7f and 7m displayed potent inhibition of both L. infantum and L. donovani. Compounds 7i and 7k exhibited selective potent inhibition of L. donovani. Especially, compounds 7e and 7k showed most potent anti-leishmanial activity against L. infantum and L. donovani respectively. Anti-leishmanial activity of these compounds is comparable with standard drugs miltefosine and pentamidine. SAR studies revealed that, electron donating group substitution on phenyl ring recommended for potent anti-leishmanial activity. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Conceptual spacecraft systems design and synthesis

    NASA Technical Reports Server (NTRS)

    Wright, R. L.; Deryder, D. D.; Ferebee, M. J., Jr.

    1984-01-01

    An interactive systems design and synthesis is performed on future spacecraft concepts using the Interactive Design and Evaluation of Advanced Systems (IDEAS) computer-aided design and analysis system. The capabilities and advantages of the systems-oriented interactive computer-aided design and analysis system are described. The synthesis of both large antenna and space station concepts, and space station evolutionary growth designs is demonstrated. The IDEAS program provides the user with both an interactive graphics and an interactive computing capability which consists of over 40 multidisciplinary synthesis and analysis modules. Thus, the user can create, analyze, and conduct parametric studies and modify earth-orbiting spacecraft designs (space stations, large antennas or platforms, and technologically advanced spacecraft) at an interactive terminal with relative ease. The IDEAS approach is useful during the conceptual design phase of advanced space missions when a multiplicity of parameters and concepts must be analyzed and evaluated in a cost-effective and timely manner.

  12. Work of community health agents in the Family Health Strategy: meta-synthesis

    PubMed Central

    Alonso, Carolina Maria do Carmo; Béguin, Pascal Daniel; Duarte, Francisco José de Castro Moura

    2018-01-01

    ABSTRACT OBJECTIVE To systematize and analyze the evidence from qualitative studies that address the perception of Brazilian Community Health Agents about their work. METHODS This is a systematic review of the meta-synthesis type on the work of community health agents, carried out from the Virtual Health Library using the descriptors “Agente Comunitário de Saúde” and “Trabalho”, in Portuguese. The strategy was constructed by crossing descriptors, using the Boolean operator “AND”, and filtering Brazilian articles, published from 2004 to 2014, which resulted in 129 identified articles. We removed quantitative or quanti-qualitative research articles, essays, debates, literature reviews, reports of experiences, and research that did not include Brazilian Community Health Agents as subjects. Using these criteria, we selected and analyzed 33 studies that allowed us to identify common subjects and differences between them, to group the main conclusions, to classify subjects, and to interpret the content. RESULTS The analysis resulted in three thematic units: characteristics of the work of community health agents, problems related to the work of community health agents, and positive aspects of the work of community health agents. On the characteristics, we could see that the work of the community health agents is permeated by the political and social dimensions of the health work with predominant use of light technologies. The main input is the knowledge that this professional obtains with the contact with families, which is developed with home visits. On the problems in the work of community health agents, we could identify the lack of limits in their attributions, poor conditions, obstacles in the relationship with the community and teams, weak professional training, and bureaucracy. The positive aspects we identified were the recognition of the work by families, resolution, bonding, work with peers, and work close to home. CONCLUSIONS This review provided

  13. Work of community health agents in the Family Health Strategy: meta-synthesis.

    PubMed

    Alonso, Carolina Maria do Carmo; Béguin, Pascal Daniel; Duarte, Francisco José de Castro Moura

    2018-01-01

    OBJECTIVE To systematize and analyze the evidence from qualitative studies that address the perception of Brazilian Community Health Agents about their work. METHODS This is a systematic review of the meta-synthesis type on the work of community health agents, carried out from the Virtual Health Library using the descriptors "Agente Comunitário de Saúde" and "Trabalho", in Portuguese. The strategy was constructed by crossing descriptors, using the Boolean operator "AND", and filtering Brazilian articles, published from 2004 to 2014, which resulted in 129 identified articles. We removed quantitative or quanti-qualitative research articles, essays, debates, literature reviews, reports of experiences, and research that did not include Brazilian Community Health Agents as subjects. Using these criteria, we selected and analyzed 33 studies that allowed us to identify common subjects and differences between them, to group the main conclusions, to classify subjects, and to interpret the content. RESULTS The analysis resulted in three thematic units: characteristics of the work of community health agents, problems related to the work of community health agents, and positive aspects of the work of community health agents. On the characteristics, we could see that the work of the community health agents is permeated by the political and social dimensions of the health work with predominant use of light technologies. The main input is the knowledge that this professional obtains with the contact with families, which is developed with home visits. On the problems in the work of community health agents, we could identify the lack of limits in their attributions, poor conditions, obstacles in the relationship with the community and teams, weak professional training, and bureaucracy. The positive aspects we identified were the recognition of the work by families, resolution, bonding, work with peers, and work close to home. CONCLUSIONS This review provided an overview of the

  14. Synthesis, Characterization, and Multimillion-Atom Simulation of Halogen-Based Energetic Materials for Agent Defeat

    DTIC Science & Technology

    2013-04-01

    DTRA-TR-13-23 Synthesis, Characterization, and Multimillion -Atom Simulation of Halogen-Based Energetic Materials for Agent Defeat Approved for...reagents for the destruction of biologically active materials and a simulation of their reactions on a multimillion atom scale with quantum...explosives for destruction of chemical & biological agents. Multimillion -atom molecular dynamics simulations with quantum mechanical accuracy were

  15. Magnetic Nanoparticles: From Design and Synthesis to Real World Applications

    PubMed Central

    Kudr, Jiri; Heger, Zbynek; Cernak, Mirko; Adam, Vojtech; Zitka, Ondrej

    2017-01-01

    The increasing number of scientific publications focusing on magnetic materials indicates growing interest in the broader scientific community. Substantial progress was made in the synthesis of magnetic materials of desired size, morphology, chemical composition, and surface chemistry. Physical and chemical stability of magnetic materials is acquired by the coating. Moreover, surface layers of polymers, silica, biomolecules, etc. can be designed to obtain affinity to target molecules. The combination of the ability to respond to the external magnetic field and the rich possibilities of coatings makes magnetic materials universal tool for magnetic separations of small molecules, biomolecules and cells. In the biomedical field, magnetic particles and magnetic composites are utilized as the drug carriers, as contrast agents for magnetic resonance imaging (MRI), and in magnetic hyperthermia. However, the multifunctional magnetic particles enabling the diagnosis and therapy at the same time are emerging. The presented review article summarizes the findings regarding the design and synthesis of magnetic materials focused on biomedical applications. We highlight the utilization of magnetic materials in separation/preconcentration of various molecules and cells, and their use in diagnosis and therapy. PMID:28850089

  16. Effect of reducing agents on low-temperature synthesis of nanostructured LiFePO4

    NASA Astrophysics Data System (ADS)

    Kulka, Andrzej; Walczak, Katarzyna; Zając, Wojciech; Molenda, Janina

    2017-09-01

    Simple co-precipitation synthesis procedure yielding nanometric LiFePO4 with enhanced electrochemical properties without any post-synthesis heat treatment is presented. XRD, SEM and TEM analysis of the obtained powders revealed platelet crystallites and well crystalized bulk structure. Effective way of decreasing amount of Fe3+ containing phases by addition of reducing agents (KI, (NH4)2S2O3, glucose and the atmosphere of 5%H2-95%Ar) during low-temperature (107 °C) synthesis is described. The traditional analytical chemistry methods or the Mӧssbauer spectroscopy methods revealed that utilization of selected reducing agents diminished Fe3+ concentration from 25 to 12 at%. The constructed cells with optimized LiFePO4 as a cathode material showed superior electrochemical performances, including high reversible capacity up to 162 mAh/g at C/10 current discharge rate, flat voltage plateau with a value close to 3.45 V vs. Li0/+.

  17. Synthesis and Bioactivity Evaluation of Novel 2-Salicyloylbenzofurans as Antibacterial Agents.

    PubMed

    Phan, Phuong-Thuy T; Nguyen, Thu-Trang T; Nguyen, Hong-Nhung T; Le, Bao-Khanh N; Vu, Thao T; Tran, Dong C; Pham, Tuan-Anh N

    2017-04-25

    In order to discover new antibacterial agents, series of 2-salicyloylbenzofuran derivatives were designed, synthesized and evaluated for their antibacterial activities against three Gram-(+) strains (methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, and Streptococcus faecalis ( S. faecalis ) ATCC 29212) and one Gram-(-) strain ( Escherichia coli (E. coli) ATCC 25922). The 2-salicyloylbenzofuran heterocycles were generated by Rap-Stoermer condensation of salicylaldehydes with phenacyl bromides and then converted to diverse O -ether derivatives by Williamson synthesis. The targeted products were screened for in vitro qualitative (zone of inhibition) and quantitative (MIC) antibacterial activities by agar well diffusion assay and agar dilution method. Amongst the compounds, those bearing carboxylic acid functional group were found to exhibit reasonable activity against Gram-(+) bacterial strains including S. faecalis , MSSA and MRSA with the most potent antibacterial agent 8h (MICs = 0.06-0.12 mM). Besides, the 2-salicyloylbenzofurans partly displayed inhibitory activity against MRSA with the best MICs = 0.14 mM ( 8f ) and 0.12 mM ( 8h ). Finally, the antibacterial results preliminarily suggested that the substituent bearing carboxylic acid group at salicyloyl-C2 and the bromine atoms on the benzofuran moiety seem to be the functionality necessary for antibacterial activities.

  18. Design and Synthesis of New Peptidomimetics as Potential Inhibitors of MurE.

    PubMed

    Zivec, Matej; Turk, Samo; Blanot, Didier; Gobec, Stanislav

    2011-03-01

    With the continuing emergence and spread of multidrug-resistant bacteria, there is an urgent need for the development of new antimicrobial agents. One possible source of new antibacterial targets is the biosynthesis of the bacterial cell-wall peptidoglycan. The assembly of the peptide stem is carried out by four essential enzymes, known as the Mur ligases (MurC, D, E and F). We have designed and synthesised a focused library of compounds as potential inhibitors of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:L-lysine ligase (MurE) from Staphylococcus aureus. This was achieved using two approaches: (i) synthesis of transition-state analogues based on the methyleneamino core; and (ii) synthesis of MurE reaction product analogues. Two methyleneamino-based compounds are identified as initial hits for inhibitors of MurE.

  19. Structural design, synthesis and substituent effect of hydrazone-N-acylhydrazones reveal potent immunomodulatory agents.

    PubMed

    Meira, Cássio S; Dos Santos Filho, José Maurício; Sousa, Caroline C; Anjos, Pâmela S; Cerqueira, Jéssica V; Dias Neto, Humberto A; da Silveira, Rafael G; Russo, Helena M; Wolfender, Jean-Luc; Queiroz, Emerson F; Moreira, Diogo R M; Soares, Milena B P

    2018-05-01

    4-(Nitrophenyl)hydrazone derivatives of N-acylhydrazone were synthesized and screened for suppress lymphocyte proliferation and nitrite inhibition in macrophages. Compared to an unsubstituted N-acylhydrazone, active compounds were identified within initial series when hydroxyl, chloride and nitro substituents were employed. Structure-activity relationship was further developed by varying the position of these substituents as well as attaching structurally-related substituents. Changing substituent position revealed a more promising compound series of anti-inflammatory agents. In contrast, an N-methyl group appended to the 4-(nitrophenyl)hydrazone moiety reduced activity. Anti-inflammatory activity of compounds is achieved by modulating IL-1β secretion and prostaglandin E2 synthesis in macrophages and by inhibiting calcineurin phosphatase activity in lymphocytes. Compound SintMed65 was advanced into an acute model of peritonitis in mice, where it inhibited the neutrophil infiltration after being orally administered. In summary, we demonstrated in great details the structural requirements and the underlying mechanism for anti-inflammatory activity of a new family of hydrazone-N-acylhydrazone, which may represent a valuable medicinal chemistry direction for the anti-inflammatory drug development in general. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Synthesis of Some Benzofuran Derivatives Containing Pyrimidine Moiety as Potent Antimicrobial Agents.

    PubMed

    Venkatesh, Talavara; Bodke, Yadav Dasharathrao; Joy, Muthipeedika Nibin; Dhananjaya, Bhadrapura Lakkappa; Venkataraman, Sivaramakrishnan

    2018-01-01

    In this investigation, the synthesis of 2-substituted pyrimidines by the reaction of benzofuran chalcones (3a-d) with urea, thiourea and guanidine hydrochloride was reported. The structures of title compounds (4a-d), (5a-d) and (6a-d) were established on the basis of analytical and spectral data. The synthesized compounds were screened for antimicrobial activity and molecular docking studies. Some of the compounds displayed excellent antimicrobial activity. The molecular docking analysis revealed that compounds 5a and 5c with the lowest binding energy in comparison to others suggesting its potential as best inhibitor of GluN-6-P. Consequently, it is confirmed from the above analysis that the compounds 5a and 5c might serve as a useful backbone scaffold for rational design, adaptation and investigation of more active analogs as potential broad spectrum antimicrobial agents.

  1. Design and Synthesis of a Novel Class of Flavonoid Derivatives via Sequential Phosphorylation and its Application for Greener Nanoparticle Synthesis

    NASA Astrophysics Data System (ADS)

    Osonga, Francis Juma

    Flavonoids exhibit arrays of biological effects that are beneficial to humans, including anti-viral, anti-oxidative, anti-inflammatory and anti-carcinogenic effects. However, these applications have been hindered by their poor stability and solubility in common solvents. Consequently, there is significant interest in the modification of flavonoids to improve their solubility. This poor solubility is also believed to be responsible for its permeability and bioavailability. Hence the central goal of this work is to design synthetic strategies for the sequential protection of the -OH groups in order to produce phosphorylated quercetin and apigenin derivatives. This work is divided into two parts: the first part presents the design, synthesis, and characterization of novel flavonoid derivatives via global and sequential phosphorylation. The second part focuses on the application of the synthesized derivatives for greener nanoparticle synthesis. This work shows for the first time that sequential phosphorylation of Quercetin is feasible through the design of 4 new derivatives namely: 5,4'-O-Quercetin Diphosphate (QDPI), 4'-O-phosphate Quercetin (4'-QPI), 5,4'-Quercetin Diphosphate (5,4'-QDP) and monophosphate 4-QP. The synthesis of 4'-QP and 5, 4'-QDP was successful with 85% and 60.5% yields respectively. In addition, the progress towards the total synthesis of apigenin phosphate derivatives (7, 4'-ADP and 7-AP) is presented. The synthesized derivatives were characterized using 1H, 13C, and 31P NMR. The phosphorylated derivatives were subsequently explored as reducing agents for sustainable synthesis of gold, silver and copper nanoparticles. We have successfully demonstrated the photochemical synthesis of gold nanoplates of sizes ranging from 10 - 200 nm using water soluble QDP in the presence of sunlight. This work contributes immensely in promoting the ideals of green nanosynthesis by (i) eliminating the use of organic solvents in the nanosynthesis, (ii) exploiting the

  2. Synthesis and biological activity of imidazopyridine anticoccidial agents: part I.

    PubMed

    Scribner, Andrew; Dennis, Richard; Hong, Jean; Lee, Shuliang; McIntyre, Donald; Perrey, David; Feng, Dennis; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

    2007-01-01

    Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we present the synthesis and biological activity of imidazo[1,2-a]pyridine anticoccidial agents. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

  3. Design and synthesis of aminocoumarin derivatives as DPP-IV inhibitors and anticancer agents.

    PubMed

    Soni, Rina; Soman, Shubhangi S

    2018-09-01

    DPP-IV "a moonlighting protein" has immerged as promising pathway to control Type 2 diabetes as well as found to play key role in earlier stages of cancer. Here we have reported design, synthesis and applications of aminocoumarin derivatives as DPP-IV inhibitors. Compounds have been synthesized and studied for their DPP-IV inhibition activity. Three compounds have shown moderate inhibition at 100 µM concentration. All compounds were also screened for their anticancer activity against A549 (Lung cancer cell line), MCF-7 (Breast cancer cell line) using MTT assay. One of the compounds has shown very good anticancer activity with IC 50 value 24 ± 0.1 nM against A549 cell line. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Controlled synthesis of flexible graphene aerogels macroscopic monolith as versatile agents for wastewater treatment

    NASA Astrophysics Data System (ADS)

    Dong, Shuying; Xia, Longji; Guo, Teng; Zhang, Fangyuan; Cui, Lingfang; Su, Xianfa; Wang, Dong; Guo, Wei; Sun, Jianhui

    2018-07-01

    Emerging applications for environmental purification require agents that not only possess high decontamination efficiency, but also are capable of withstanding mechanical deformation without secondary pollution and degradation of performance. To this end, we have controlled synthesis of mechanically flexible graphene aerogel (GA) by vacuum freeze-drying of their hydrogel precursors obtained from heating the aqueous mixtures of graphene oxide (GO) and Vitamin C (VC) without stirring. Through the adaptable process conditions, such as the particle size of carbon, GO concentration, dosage of reducing agent and solution pH, the highly porous, ultralight and mechanically flexible GA are synthesized. Owing to the porous, robust and stable structure, the resulting GA show very promising performance in water purification including enrichment of organic liquid solvents (alcohols, oil and alkanes), removal of hexavalent chromium Cr(VI) and purified industrial wastewater, as well as flexible conductors. The successful creation of the GA may provide new insights into the design of carbon-based aerogels for various applications, as the GA can be prepared via a very simple procedure and available in macroscopic diverse morphologies with tunable porosity.

  5. Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents.

    PubMed

    Luo, Wen; Wang, Ting; Hong, Chen; Yang, Ya-Chen; Chen, Ying; Cen, Juan; Xie, Song-Qiang; Wang, Chao-Jie

    2016-10-21

    A new series of 4-dimethylamine flavonoid derivatives were designed and synthesized as potential multifunctional anti-Alzheimer agents. The inhibition of cholinesterase activity, self-induced β-amyloid (Aβ) aggregation, and antioxidant activity by these derivatives was investigated. Most of the compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. A Lineweaver-Burk plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. The derivatives showed potent self-induced Aβ aggregation inhibition and peroxyl radical absorbance activity. Moreover, compound 6d significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Thus, these compounds could become multifunctional agents for further development for the treatment of AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Rational design and synthesis of 2-anilinopyridinyl-benzothiazole Schiff bases as antimitotic agents.

    PubMed

    Shaik, Thokhir B; Hussaini, S M Ali; Nayak, V Lakshma; Sucharitha, M Lakshmi; Malik, M Shaheer; Kamal, Ahmed

    2017-06-01

    Based on our previous results and literature precedence, a series of 2-anilinopyridinyl-benzothiazole Schiff bases were rationally designed by performing molecular modeling experiments on some selected molecules. The binding energies of the docked molecules were better than the E7010, and the Schiff base with trimethoxy group on benzothiazole moiety, 4y was the best. This was followed by the synthesis of a series of the designed molecules by a convenient synthetic route and evaluation of their anticancer potential. Most of the compounds have shown significant growth inhibition against the tested cell lines and the compound 4y exhibited good antiproliferative activity with a GI 50 value of 3.8µM specifically against the cell line DU145. In agreement with the docking results, 4y exerted cytotoxicity by the disruption of the microtubule dynamics by inhibiting tubulin polymerization via effective binding into colchicine domain, comparable to E7010. Detailed binding modes of 4y with colchicine binding site of tubulin were studied by molecular docking. Furthermore, 4y induced apoptosis as evidenced by biological studies like mitochondrial membrane potential, caspase-3, and Annexin V-FITC assays. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Design, Synthesis and Testing of Novel Antimalarial

    DTIC Science & Technology

    2006-05-05

    U.S.N.A. --- Trident Scholar project report; no. 343 (2006) DESIGN, SYNTHESIS AND TESTING OF NOVEL ANTIMALARIAL COMPOUNDS by Midshipman 1/C...Certification of Adviser Approval Assistant Professor Clare E. Gutteridge Chemistry Department ____________________________________ (signature...Leave blank) 2. REPORT DATE 5 May 2006 3. REPORT TYPE AND DATE COVERED 4. TITLE AND SUBTITLE Design, synthesis and testing of

  8. Modeling agent's preferences by its designer's social value orientation

    NASA Astrophysics Data System (ADS)

    Zuckerman, Inon; Cheng, Kan-Leung; Nau, Dana S.

    2018-03-01

    Human social preferences have been shown to play an important role in many areas of decision-making. There is evidence from the social science literature that human preferences in interpersonal interactions depend partly on a measurable personality trait called, Social Value Orientation (SVO). Automated agents are often written by humans to serve as their delegates when interacting with other agents. Thus, one might expect an agent's behaviour to be influenced by the SVO of its human designer. With that in mind, we present the following: first, we explore, discuss and provide a solution to the question of how SVO tests that were designed for humans can be used to evaluate agents' social preferences. Second, we show that in our example domain there is a medium-high positive correlation between the social preferences of agents and their human designers. Third, we exemplify how the SVO information of the designer can be used to improve the performance of some other agents playing against those agents, and lastly, we develop and exemplify the behavioural signature SVO model which allows us to better predict performances when interactions are repeated and behaviour is adapted.

  9. Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.

    PubMed

    Ashraf, Zaman; Bais, Abdul; Manir, Md Maniruzzaman; Niazi, Umar

    2015-01-01

    A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.

  10. Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies

    PubMed Central

    Ashraf, Zaman; Bais, Abdul; Manir, Md. Maniruzzaman; Niazi, Umar

    2015-01-01

    A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents. PMID:26267242

  11. Design, synthesis, and biological evaluation of the first podophyllotoxin analogues as potential vascular-disrupting agents.

    PubMed

    Labruère, Raphaël; Gautier, Benoît; Testud, Marlène; Seguin, Johanne; Lenoir, Christine; Desbène-Finck, Stéphanie; Helissey, Philippe; Garbay, Christiane; Chabot, Guy G; Vidal, Michel; Giorgi-Renault, Sylviane

    2010-12-03

    We designed and synthesized two novel series of azapodophyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moieties; in the second series, conformational restriction of the E nucleus was considered. We have identified several new compounds with inhibitory activity toward tubulin polymerization similar to that of CA-4 and colchicine, while displaying low cytotoxic activity against normal and/or cancer cells. An aminologue and a methylenic analogue were shown to disrupt endothelial cell cords on Matrigel at subtoxic concentrations, and an original assay of drug washout allowed us to demonstrate the rapid reversibility of this effect. These two new analogues are promising leads for the development of vascular-disrupting agents in the podophyllotoxin series.

  12. Design, Synthesis and Biological Evaluation of Novel Phosphorylated Abacavir Derivatives as Antiviral Agents Against Newcastle Disease Virus Infection in Chicken.

    PubMed

    K A, Suresh; Venkata Subbaiah, Kadiam C; Lavanya, Rayapu; Chandrasekhar, Kuruva; Chamarti, Naga Raju; Kumar, M Suresh; Wudayagiri, Rajendra; Valluru, Lokanatha

    2016-09-01

    Newcastle disease virus is the most devastating virus in poultry industry. It can eradicate the entire poultry flocks once infected. This study is aimed to investigate the antiviral efficacy of novel phosphorylated analogues of the drug abacavir (ABC) against Newcastle disease virus (NDV). About 16 analogues of ABC were designed and docking was performed against fusion protein of NDV. Three compounds were identified and selected for synthesis and biological evaluation based on binding affinity and docking scores. The compounds were synthesized and characterized by IR, (1)H, (13)C, (31)P and CHN analysis and mass spectra. These compounds were tested for antiviral efficacy against NDV-infected DF-1 cells. Compound ABC-1 had shown potent antiviral activity as evidenced by significant reduction in plaque units and cytopathic effect. Therefore, ABC-1 was selected to test for NDV-infected chicken survival rate. Effective dose50 concentrations were determined for ABC-1. Antioxidant enzyme levels in brain, liver and lung tissues were estimated. Superoxide dismutase and catalase were significantly raised and lipid peroxidation and HA titer levels were decreased upon treatment with 2 mg/kg body weight ABC-1. Histopathological modifications were also restored in the ABC-1-treated group. These findings demonstrated ABC-1 as a potential antiviral agent against NDV in chicken.

  13. Designing Distributed Learning Environments with Intelligent Software Agents

    ERIC Educational Resources Information Center

    Lin, Fuhua, Ed.

    2005-01-01

    "Designing Distributed Learning Environments with Intelligent Software Agents" reports on the most recent advances in agent technologies for distributed learning. Chapters are devoted to the various aspects of intelligent software agents in distributed learning, including the methodological and technical issues on where and how intelligent agents…

  14. Intelligent Design of Nano-Scale Molecular Imaging Agents

    PubMed Central

    Kim, Sung Bae; Hattori, Mitsuru; Ozawa, Takeaki

    2012-01-01

    Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs), biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on–off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents. PMID:23235326

  15. Intelligent design of nano-scale molecular imaging agents.

    PubMed

    Kim, Sung Bae; Hattori, Mitsuru; Ozawa, Takeaki

    2012-12-12

    Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs), biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on-off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents.

  16. 30 CFR 550.145 - How do I designate an agent or a local agent?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... designate an agent empowered to fulfill your obligations under the Act, the lease, or the regulations in... local agent empowered to receive notices and submit requests, applications, notices, or supplemental...

  17. 30 CFR 550.145 - How do I designate an agent or a local agent?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... designate an agent empowered to fulfill your obligations under the Act, the lease, or the regulations in... local agent empowered to receive notices and submit requests, applications, notices, or supplemental...

  18. 30 CFR 550.145 - How do I designate an agent or a local agent?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... designate an agent empowered to fulfill your obligations under the Act, the lease, or the regulations in... local agent empowered to receive notices and submit requests, applications, notices, or supplemental...

  19. 30 CFR 250.145 - How do I designate an agent or a local agent?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Director may require you to designate an agent empowered to fulfill your obligations under the Act, the... Regional Supervisor's approval a local agent empowered to receive notices and submit requests, applications...

  20. Designing Agent Utilities for Coordinated, Scalable and Robust Multi-Agent Systems

    NASA Technical Reports Server (NTRS)

    Tumer, Kagan

    2005-01-01

    Coordinating the behavior of a large number of agents to achieve a system level goal poses unique design challenges. In particular, problems of scaling (number of agents in the thousands to tens of thousands), observability (agents have limited sensing capabilities), and robustness (the agents are unreliable) make it impossible to simply apply methods developed for small multi-agent systems composed of reliable agents. To address these problems, we present an approach based on deriving agent goals that are aligned with the overall system goal, and can be computed using information readily available to the agents. Then, each agent uses a simple reinforcement learning algorithm to pursue its own goals. Because of the way in which those goals are derived, there is no need to use difficult to scale external mechanisms to force collaboration or coordination among the agents, or to ensure that agents actively attempt to appropriate the tasks of agents that suffered failures. To present these results in a concrete setting, we focus on the problem of finding the sub-set of a set of imperfect devices that results in the best aggregate device. This is a large distributed agent coordination problem where each agent (e.g., device) needs to determine whether to be part of the aggregate device. Our results show that the approach proposed in this work provides improvements of over an order of magnitude over both traditional search methods and traditional multi-agent methods. Furthermore, the results show that even in extreme cases of agent failures (i.e., half the agents failed midway through the simulation) the system's performance degrades gracefully and still outperforms a failure-free and centralized search algorithm. The results also show that the gains increase as the size of the system (e.g., number of agents) increases. This latter result is particularly encouraging and suggests that this method is ideally suited for domains where the number of agents is currently in the

  1. 30 CFR 250.145 - How do I designate an agent or a local agent?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... require you to designate an agent empowered to fulfill your obligations under the Act, the lease, or the... approval a local agent empowered to receive notices and submit requests, applications, notices, or...

  2. 30 CFR 250.145 - How do I designate an agent or a local agent?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... require you to designate an agent empowered to fulfill your obligations under the Act, the lease, or the... approval a local agent empowered to receive notices and submit requests, applications, notices, or...

  3. 30 CFR 250.145 - How do I designate an agent or a local agent?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... require you to designate an agent empowered to fulfill your obligations under the Act, the lease, or the... approval a local agent empowered to receive notices and submit requests, applications, notices, or...

  4. [Synthesis of 1-substituted nitroimidazoles and its evaluation as radiosensitizing agents].

    PubMed

    Adams, D R; Martul, R; Alvarez, M V; López Zumel, M C; Espada, M

    1991-01-01

    The synthesis of various substituted nitroimidazoles with lipophilic and hydrophilic side chains as potential radiosensitizing agents is described. The starting material employed was 4(5)-nitroimidazole, which was alkylated via the sodium salt with various chloro-methylated, substituted alcohols and esters, in order to obtain analogues of misonidazole, metronidazole and desmethylmisonidazole of known radiosensitizing and bactericidal activity. Some final products were assayed for their radiosensitizing properties giving negative results under the testing conditions used.

  5. Design and synthesis of some new pyrazolyl-pyrazolines as potential anti-inflammatory, analgesic and antibacterial agents.

    PubMed

    Viveka, Shivapura; Dinesha; Shama, Prasanna; Nagaraja, Gundibasappa Karikannar; Ballav, Shuvankar; Kerkar, Savita

    2015-08-28

    In the present study, an efficient synthesis of some new substituted pyrazoline derivatives linked to a substituted pyrazole scaffold was performed by a multistep reaction sequences and compounds were screened for their anti-inflammatory, analgesic and antibacterial activities. The preliminary results revealed that the N-acylated (5e, 5h) and nitro substituted N-phenyl (6f) pyrazolyl-pyrazolines derivatives exhibited a very promising anti-inflammatory activity whereas 5h, 6f were interesting analgesic agents. The compounds with halo substituted phenyl group at C-3 of the pyrazoline ring (4a, 5g, 5h, 6a and 6b) were found to be active against clinical bacterial pathogens with MIC in the range of 0.2-0.4 mg/mL. Compound containing N-propionyl pyrazolyl-pyrazoline (5h) could be identified as the most active member within this study with a dual anti-inflammatory and antibacterial profile. Taken together, this study has led to the development of promising compounds. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. 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

  7. Synthesis of Triazole Derivatives of Levoglucosenone As Promising Anticancer Agents: Effective Exploration of the Chemical Space through retro-aza-Michael//aza-Michael Isomerizations.

    PubMed

    Tsai, Yi-Hsuan; Borini Etichetti, Carla M; Di Benedetto, Carolina; Girardini, Javier E; Martins, Felipe Terra; Spanevello, Rolando A; Suárez, Alejandra G; Sarotti, Ariel M

    2018-04-06

    The design and synthesis of biomass-derived triazoles and the in vitro evaluation as potential anticancer agents are described. The discovery of base-catalyzed retro-aza-Michael//aza-Michael isomerizations allowed the exploration of the chemical space by affording novel types of triazoles, difficult to obtain otherwise. Following this strategy, 2,4-disubstituted 1,2,3-triazoles could be efficiently obtained from the corresponding 1,4-disubstituted analogues.

  8. Design and synthesis of some new 2,3'-bipyridine-5-carbonitriles as potential anti-inflammatory/antimicrobial agents.

    PubMed

    Elzahhar, Perihan A; Elkazaz, Salwa; Soliman, Raafat; El-Tombary, Alaa A; Shaltout, Hossam A; El-Ashmawy, Ibrahim M; Abdel Wahab, Abeer E; El-Hawash, Soad A

    2017-08-01

    Inflammation may cause accumulation of fluid in the injured area, which may promote bacterial growth. Other reports disclosed that non-steroidal anti-inflammatory drugs may enhance progression of bacterial infection. This work describes synthesis of new series of 2,3'-bipyridine-5-carbonitriles as structural analogs of etoricoxib, linked at position-6 to variously substituted thio or oxo moieties. Biological screening results revealed that compounds 2b, 4b, 7e and 8 showed significant acute and chronic AI activities and broad spectrum of antimicrobial activity. In addition, similarity ensemble approach was applied to predict potential biological targets of the tested compounds. Then, pharmacophore modeling study was employed to determine the most important structural parameters controlling bioactivity. Moreover, title compounds showed physicochemical properties within those considered adequate for drug candidates. This study explored the potential of such series of compounds as structural leads for further modification to develop a new class of dual AI-antimicrobial agents.

  9. Synthesis of surface bound silver nanoparticles on cellulose fibers using lignin as multi-functional agent.

    PubMed

    Hu, Sixiao; Hsieh, You-Lo

    2015-10-20

    Lignin has proven to be highly effective "green" multi-functional binding, complexing and reducing agents for silver cations as well as capping agents for the synthesis of silver nanoparticles on ultra-fine cellulose fibrous membranes. Silver nanoparticles could be synthesized in 10min to be densely distributed and stably bound on the cellulose fiber surfaces at up to 2.9% in mass. Silver nanoparticle increased in sizes from 5 to 100nm and became more polydispersed in size distribution on larger fibers and with longer synthesis time. These cellulose fiber bound silver nanoparticles did not agglomerate under elevated temperatures and showed improved thermal stability. The presence of alkali lignin conferred moderate UV absorbing ability in both UV-B and UV-C regions whereas the bound silver nanoparticles exhibited excellent antibacterial activities toward Escherichia coli. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Ascorbyl coumarates as multifunctional cosmeceutical agents that inhibit melanogenesis and enhance collagen synthesis.

    PubMed

    Kwak, Jun Yup; Park, Soojin; Seok, Jin Kyung; Liu, Kwang-Hyeon; Boo, Yong Chool

    2015-09-01

    L-Ascorbic acid (AA) and p-coumaric acid (p-CA) are naturally occurring antioxidants that are known to enhance collagen synthesis and inhibit melanin synthesis, respectively. The purpose of this study was to examine hybrid compounds between AA and p-CA as multifunctional cosmeceutical agents. Ascorbyl 3-p-coumarate (A-3-p-C), ascorbyl 2-p-coumarate (A-2-p-C), and their parent compounds were tested for their effects on cellular melanin synthesis and collagen synthesis. At 100 μM, A-3-p-C and A-2-p-C decreased melanin content of human dermal melanocytes stimulated by L-tyrosine, by 65 and 59%, respectively, compared to 11% inhibition of AA and 70% inhibition of p-CA. A-3-p-C and A-2-p-C were less effective than p-CA but more effective than AA at inhibiting tyrosinase activity. A-3-p-C and A-2-p-C were more effective than p-CA at inhibiting the autoxidation of L-3,4-dihydroxyphenylalanine. At 100-300 μM, A-3-p-C and A-2-p-C augmented collagen release from human dermal fibroblasts by 120-144% and 125-191%, respectively, compared to 126-133% increase of AA and 120-146% increase of p-CA. They increased procollagen type I C-peptide release (A-3-p-C, and A-2-p-C) like AA, and decreased matrix metalloproteinase 1 level (A-2-p-C) like p-CA, implicating that they might regulate collagen metabolism by multiple mechanisms. This study suggests that A-3-p-C and A-2-p-C could be used as multifunctional cosmeceutical agents for the attenuation of certain aspects of skin aging.

  11. The Design of Motivational Agents and Avatars

    ERIC Educational Resources Information Center

    Baylor, Amy L.

    2011-01-01

    While the addition of an anthropomorphic interface agent to a learning system generally has little direct impact on learning, it potentially has a huge impact on learner motivation. As such agents become increasingly ubiquitous on the Internet, in virtual worlds, and as interfaces for learning and gaming systems, it is important to design them to…

  12. New frontiers in design synthesis

    NASA Technical Reports Server (NTRS)

    Goldin, D. S.; Venneri, S. L.; Noor, A. K.

    1999-01-01

    The Intelligent Synthesis Environment (ISE), which is one of the major strategic technologies under development at NASA centers and the University of Virginia, is described. One of the major objectives of ISE is to significantly enhance the rapid creation of innovative affordable products and missions. ISE uses a synergistic combination of leading-edge technologies, including high performance computing, high capacity communications and networking, human-centered computing, knowledge-based engineering, computational intelligence, virtual product development, and product information management. The environment will link scientists, design teams, manufacturers, suppliers, and consultants who participate in the mission synthesis as well as in the creation and operation of the aerospace system. It will radically advance the process by which complex science missions are synthesized, and high-tech engineering Systems are designed, manufactured and operated. The five major components critical to ISE are human-centered computing, infrastructure for distributed collaboration, rapid synthesis and simulation tools, life cycle integration and validation, and cultural change in both the engineering and science creative process. The five components and their subelements are described. Related U.S. government programs are outlined and the future impact of ISE on engineering research and education is discussed.

  13. "Basic MR Relaxation Mechanisms & Contrast Agent Design"

    PubMed Central

    De León-Rodríguez, Luis M.; Martins, André F.; Pinho, Marco; Rofsky, Neil; Sherry, A. Dean

    2015-01-01

    The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we will detail the many important considerations when pursuing the design and use of MR contrast media. We will offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand based contrast agents. We will discuss the mechanisms involved in magnetic resonance relaxation in the context of probe design strategies. A brief description of currently available contrast agents will be accompanied by an in-depth discussion that highlights promising MRI contrast agents in development for future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. PMID:25975847

  14. Finite element design for the HPHT synthesis of diamond

    NASA Astrophysics Data System (ADS)

    Li, Rui; Ding, Mingming; Shi, Tongfei

    2018-06-01

    The finite element method is used to simulate the steady-state temperature field in diamond synthesis cell. The 2D and 3D models of the China-type cubic press with large deformation of the synthesis cell was established successfully, which has been verified by situ measurements of synthesis cell. The assembly design, component design and process design for the HPHT synthesis of diamond based on the finite element simulation were presented one by one. The temperature field in a high-pressure synthetic cavity for diamond production is optimized by adjusting the cavity assembly. A series of analysis about the influence of the pressure media parameters on the temperature field are examined through adjusting the model parameters. Furthermore, the formation mechanism of wasteland was studied in detail. It indicates that the wasteland is inevitably exists in the synthesis sample, the distribution of growth region of the diamond with hex-octahedral is move to the center of the synthesis sample from near the heater as the power increasing, and the growth conditions of high quality diamond is locating at the center of the synthesis sample. These works can offer suggestion and advice to the development and optimization of a diamond production process.

  15. Axinellamines as Broad-Spectrum Antibacterial Agents: Scalable Synthesis and Biology

    PubMed Central

    2015-01-01

    Antibiotic-resistant bacteria present an ongoing challenge to both chemists and biologists as they seek novel compounds and modes of action to out-maneuver continually evolving resistance pathways, especially against Gram-negative strains. The dimeric pyrrole–imidazole alkaloids represent a unique marine natural product class with diverse primary biological activity and chemical architecture. This full account traces the strategy used to develop a second-generation route to key spirocycle 9, culminating in a practical synthesis of the axinellamines and enabling their discovery as broad-spectrum antibacterial agents, with promising activity against both Gram-positive and Gram-negative bacteria. While their detailed mode of antibacterial action remains unclear, the axinellamines appear to cause secondary membrane destabilization and impart an aberrant cellular morphology consistent with the inhibition of normal septum formation. This study serves as a rare example of a natural product initially reported to be devoid of biological activity surfacing as an active antibacterial agent with an intriguing mode of action. PMID:25328977

  16. Facile One-Pot Synthesis of Tellurium Nanorods as Antioxidant and Anticancer Agents.

    PubMed

    Huang, Wei; Wu, Hualian; Li, Xiaoling; Chen, Tianfeng

    2016-08-19

    Nanorods have been utilized in targeted therapy, controlled release, molecular diagnosis, and molecule imaging owing to their large surface area and optical, magnetic, electronic, and structural properties. However, low stability and complex synthetic methods have substantially limited the application of tellurium nanorods for use as antioxidant and anticancer agents. Herein, a facile one-pot synthesis of functionalized tellurium nanorods (PTNRs) by using a hydrothermal synthetic system with a polysaccharide-protein complex (PTR), which was extracted from Pleurotus tuber-regium, as a capping agent is described. PTNRs remained stable in water and in phosphate-buffered saline and exhibited high hemocompatibility. Interestingly, these nanorods possessed strong antioxidant activity for scavenging 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS(.+) ) and 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH) free radicals and demonstrated novel anticancer activities. However, these nanorods exhibited low cytotoxicity toward normal human cells. In addition, the PTNRs effectively induced a decrease in the mitochondrial membrane potential in a dose-dependent manner, which indicated that mitochondrial dysfunction might play an important role in PTNR-induced apoptosis. Therefore, this study provides a one-pot strategy for the facile synthesis of tellurium nanorods with novel antioxidant and anticancer application potentials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Design, Synthesis, and Properties of a Potent Inhibitor of Pseudomonas aeruginosa Deacetylase LpxC.

    PubMed

    Piizzi, Grazia; Parker, David T; Peng, Yunshan; Dobler, Markus; Patnaik, Anup; Wattanasin, Som; Liu, Eugene; Lenoir, Francois; Nunez, Jill; Kerrigan, John; McKenney, David; Osborne, Colin; Yu, Donghui; Lanieri, Leanne; Bojkovic, Jade; Dzink-Fox, JoAnn; Lilly, Maria-Dawn; Sprague, Elizabeth R; Lu, Yipin; Wang, Hongming; Ranjitkar, Srijan; Xie, Lili; Wang, Bing; Glick, Meir; Hamann, Lawrence G; Tommasi, Ruben; Yang, Xia; Dean, Charles R

    2017-06-22

    Over the past several decades, the frequency of antibacterial resistance in hospitals, including multidrug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC. We approached this through the design, synthesis, and biological evaluation of novel hydroxamic acid LpxC inhibitors, exemplified by 1, where cytotoxicity against mammalian cell lines was reduced, solubility and plasma-protein binding were improved while retaining potent anti-pseudomonal activity in vitro and in vivo.

  18. Design and synthesis of novel N-benzylidenesulfonohydrazide inhibitors of MurC and MurD as potential antibacterial agents.

    PubMed

    Frlan, Rok; Kovac, Andreja; Blanot, Didier; Gobec, Stanislav; Pecar, Slavko; Obreza, Ales

    2008-01-11

    A series of novel N-benzylidenesulfonohydrazide compounds were designed and synthesized as inhibitors of UDP-N-acetylmuramic acid: L-alanine ligase (MurC) and UDP-N-acetylmuramoyl-L-alanine: D-glutamate ligase (MurD) from E. coli, involved in the biosynthesis of bacterial cell-walls. Some compounds possessed inhibitory activity against both enzymes with IC(50) values as low as 30 microM. In addition, a new, one-pot synthesis of amidobenzaldehydes is reported.

  19. Design and assembly of new non-viral RNAi delivery agents by microwave-assisted quaternization (MAQ) of tertiary amines

    PubMed Central

    Ghosh, Animesh; Mukherjee, Koushik; Jiang, Xinpeng; Zhou, Ying; McCarroll, Joshua; Qu, James; Swain, Pamela M.; Baigude, Huricha; Rana, Tariq M.

    2010-01-01

    RNA interference (RNAi), a gene-silencing phenomenon whereby double-stranded RNA (dsRNA) triggers the sequence-specific degradation of homologous mRNA. RNAi has been quickly and widely applied to discover gene functions and holds great potential to provide a new class of therapeutic agents. However, new chemistry and delivery approaches are greatly needed to silence disease-causing genes without toxic effects. We reasoned that conjugation of the cholesterol moiety to cationic lipids would enhance RNAi efficiencies and lower the toxic effects of lipid-mediated RNAi delivery. Here, we report the first design and synthesis of new cholesterol-conjugated cationic lipids for RNAi delivery using microwave-assisted quaternization (MAQ) of tertiary amines. This strategy can be employed to develop new classes of non-viral gene delivery agents under safe and fast reaction conditions. PMID:20722369

  20. Primary screen for potential sheep scab control agents.

    PubMed

    Dunn, J A; Prickett, J C; Collins, D A; Weaver, R J

    2016-07-15

    The efficacy of potential acaricidal agents were assessed against the sheep scab mite Psoroptes ovis using a series of in vitro assays in modified test arenas designed initially to maintain P. ovis off-host. The mortality effects of 45 control agents, including essential oils, detergents, desiccants, growth regulators, lipid synthesis inhibitors, nerve action/energy metabolism disruptors and ecdysteroids were assessed against adults and nymphs. The most effective candidates were the desiccants (diatomaceous earth, nanoclay and sorex), the growth regulators (buprofezin, hexythiazox and teflubenzuron), the lipid synthesis inhibitors (spirodiclofen, spirotetramat and spiromesifen) and the nerve action and energy metabolism inhibitors (fenpyroximate, spinosad, tolfenpyrad, and chlorantraniliprole). Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  1. Samarium Diiodide-Mediated Reactions in Total Synthesis

    PubMed Central

    Nicolaou, K. C.; Ellery, Shelby P.; Chen, Jason S.

    2009-01-01

    Introduced by Henri Kagan more than three decades ago, samarium diiodide (SmI2) has found increasing applications in chemical synthesis. This single-electron reducing agent has been particularly useful in C–C bond formations, including those found in total synthesis endeavors. This Review highlights selected applications of SmI2 in total synthesis, with special emphasis on novel transformations and mechanistic considerations. The examples discussed are both illustrative of the power of this reagent in complex molecule construction and inspirational for the design of synthetic strategies toward such targets, both natural and designed. PMID:19714695

  2. Interactive systems design and synthesis of future spacecraft concepts

    NASA Technical Reports Server (NTRS)

    Wright, R. L.; Deryder, D. D.; Ferebee, M. J., Jr.

    1984-01-01

    An interactive systems design and synthesis is performed on future spacecraft concepts using the Interactive Design and Evaluation of Advanced spacecraft (IDEAS) computer-aided design and analysis system. The capabilities and advantages of the systems-oriented interactive computer-aided design and analysis system are described. The synthesis of both large antenna and space station concepts, and space station evolutionary growth is demonstrated. The IDEAS program provides the user with both an interactive graphics and an interactive computing capability which consists of over 40 multidisciplinary synthesis and analysis modules. Thus, the user can create, analyze and conduct parametric studies and modify Earth-orbiting spacecraft designs (space stations, large antennas or platforms, and technologically advanced spacecraft) at an interactive terminal with relative ease. The IDEAS approach is useful during the conceptual design phase of advanced space missions when a multiplicity of parameters and concepts must be analyzed and evaluated in a cost-effective and timely manner.

  3. Diastereoselective Synthesis of a Strawberry Flavoring Agent by Epoxidation of Ethyl trans-b-Methylcinnamate

    NASA Astrophysics Data System (ADS)

    Pageau, Gayle J.; Mabaera, Rodwell; Kosuda, Kathryn M.; Sebelius, Tamara A.; Ghaffari, Ali H.; Kearns, Kenneth A.; McIntyre, Jean P.; Beachy, Tina M.; Thamattoor, Dasan M.

    2002-01-01

    The diastereoselective synthesis of ethyl (E)-3-methyl-3-phenylglycidate, a strawberry flavoring agent, is carried out by epoxidizing ethyl trans-b-methylcinnamate with m-chloroperbenzoic acid. This epoxidation is appropriate for the introductory organic laboratory and augments the small number of such experiments currently available for undergraduate education. In the course of performing this exercise, students are exposed to many important facets of organic chemistry such as synthesis, reaction mechanism, stereochemistry, chromatography, quantitative analysis, spectroscopy, and computational chemistry. The 1H NMR spectrum of this compound is especially interesting and presents instructive examples of diastereotopic protons and shielding effects of the aromatic ring current.

  4. 15 CFR 16.9 - Rules governing designated agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... representation; and (3) Agree to service any participant in this program in the agent's cognizant product area... participants that the designated agent services under the program. The Secretary shall also be provided an... transmit those fees and charges required under § 16.6 to the Secreatry; (3) Distribute Department of...

  5. 15 CFR 16.9 - Rules governing designated agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... representation; and (3) Agree to service any participant in this program in the agent's cognizant product area... participants that the designated agent services under the program. The Secretary shall also be provided an... transmit those fees and charges required under § 16.6 to the Secreatry; (3) Distribute Department of...

  6. The application of click chemistry in the synthesis of agents with anticancer activity

    PubMed Central

    Ma, Nan; Wang, Ying; Zhao, Bing-Xin; Ye, Wen-Cai; Jiang, Sheng

    2015-01-01

    The copper(I)-catalyzed 1,3-dipolar cycloaddition between alkynes and azides (click chemistry) to form 1,2,3-triazoles is the most popular reaction due to its reliability, specificity, and biocompatibility. This reaction has the potential to shorten procedures, and render more efficient lead identification and optimization procedures in medicinal chemistry, which is a powerful modular synthetic approach toward the assembly of new molecular entities and has been applied in anticancer drugs discovery increasingly. The present review focuses mainly on the applications of this reaction in the field of synthesis of agents with anticancer activity, which are divided into four groups: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, and antimicrotubule agents. PMID:25792812

  7. Design, synthesis and biological evaluation of LX2343 derivatives as neuroprotective agents for the treatment of Alzheimer's disease.

    PubMed

    Sun, Guanglong; Wang, Junwei; Guo, Xiaodan; Lei, Min; Zhang, Yinan; Wang, Xiachang; Shen, Xu; Hu, Lihong

    2018-02-10

    A series of LX2343 derivatives were designed, synthesized and evaluated as neuroprotective agents for Alzheimer's disease (AD) in vitro. Most of the compounds displayed potent neuroprotective activities. Especially for compound A6, exhibited a remarkable EC 50 value of 0.22 μM. Further investigation demonstrated that compound A6 can significantly reduce Aβ production and increase Aβ clearance, and alleviate Tau hyperphosphorylation. Most importantly, compound A6 could ameliorate learning and memory impairments in APP/PS1 transgenic mice. The present study evidently showed that compound A6 is a potent neuroprotective agent and might serve as a promising lead candidate for the treatment of Alzheimer's disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  8. The synthesis method for design of electron flow sources

    NASA Astrophysics Data System (ADS)

    Alexahin, Yu I.; Molodozhenzev, A. Yu

    1997-01-01

    The synthesis method to design a relativistic magnetically - focused beam source is described in this paper. It allows to find a shape of electrodes necessary to produce laminar space charge flows. Electron guns with shielded cathodes designed with this method were analyzed using the EGUN code. The obtained results have shown the coincidence of the synthesis and analysis calculations [1]. This method of electron gun calculation may be applied for immersed electron flows - of interest for the EBIS electron gun design.

  9. Synthesis and crystal structures of gold nanowires with Gemini surfactants as directing agents.

    PubMed

    Xu, Feng; Hou, Hao; Gao, Zhinong

    2014-12-15

    The preparation of crystalline gold nanowires (NWs) by using gemini surfactants as directing agents through a three-step seed-mediated method is reported. Unlike the nanorods with relatively low aspect ratios (typically below 20) obtained by using cetyltrimethylammonium bromide as a directing agent, the NWs obtained in this investigation can reach up to 4.4 μm, and the largest aspect ratio is calculated to be 210. For this, each of seven different gemini surfactants are utilized as directing agents, and the length and/or aspect ratio of the NWs can be tuned by varying the hydrocarbon chain lengths of the gemini surfactants. Both single and twinned crystalline structures are elucidated by selected-area electron diffraction and high-resolution transmission electron microscopy studies. The use of gemini surfactants not only advances the synthesis of gold nanostructures, but improves the understanding of the growth mechanism for seed-mediated growth. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Benzoin Schiff Bases: Design, Synthesis, and Biological Evaluation as Potential Antitumor Agents.

    PubMed

    Sabbah, Dima A; Al-Tarawneh, Fatima; Talib, Wamidh H; Sweidan, Kamal; Bardaweel, Sanaa K; Al-Shalabi, Eveen; Zhong, Haizhen A; Abu Sheikha, Ghassan; Abu Khalaf, Reema; Mubarak, Mohammad S

    2018-04-12

    Phosphoinositide 3-kinase α (PI3Kα) is an attractive target for anticancer drug design. Target compounds were designed to probe the significance of alcohol and imine moieties tailored on a benzoin scaffold to better understand the structure activity relation (SAR) and improve their biological activity as anticancer compounds. Chemical synthesis of the targeted compounds, biological evaluation tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, as well as Glide docking studies were employed in this investigation. A new series of 1,2-diphenylimino ethanol was successfully synthesized and characterized by means of FT-IR, HRMS, NMR, and by elemental analysis. Biological screening revealed that the newly synthesized compounds inhibit PI3Kα activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines. Results additionally showed that these compounds exhibit selective antiproliferative activity, induce apoptosis, and suppress the VEGF production. Compounds 2b, 2d, and 2g displayed promising inhibitory activity in HCT-116 suggesting that hydrophobic and/or hydrogen bond-acceptor mediate(s) ligand-receptor interaction on o- and m-positions. Furthermore, compounds 2g, 2i, 2j, and 2h, bearing hydrophobic moiety on m- and p-position, exerted high antiproliferative activity in T47D and MCF-7 cells, whereas compound 2e showed selectivity against T47D and MCF-7. Molecular docking studies against PI3Kα and caspase-3 demonstrated a strong correlation between the predicted binding affinity (ΔGobsd) and IC50 values of prepared compounds for the caspase-3 model, implying that the cellulous inhibitory activity was caspase-3-dependent. Moreover, Glide docking against PI3Kα identified Ser774, Lys802, E849, V851, and Asp933 as key binding residues. The series exerted a potential PI3Kα inhibitory activity in human carcinoma cell lines expressing PI3K

  11. Basic MR relaxation mechanisms and contrast agent design.

    PubMed

    De León-Rodríguez, Luis M; Martins, André F; Pinho, Marco C; Rofsky, Neil M; Sherry, A Dean

    2015-09-01

    The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists, largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we detail the many important considerations when pursuing the design and use of MR contrast media. We offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand-based contrast agents. We discuss the mechanisms involved in MR relaxation in the context of probe design strategies. A brief description of currently available contrast agents is accompanied by an in-depth discussion that highlights promising MRI contrast agents in the development of future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. © 2015 Wiley Periodicals, Inc.

  12. MIDAS: A Practical Bayesian Design for Platform Trials with Molecularly Targeted Agents

    PubMed Central

    Yuan, Ying; Guo, Beibei; Munsell, Mark; Lu, Karen; Jazaeri, Amir

    2016-01-01

    Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time, and thus not efficient for this task. We propose a Bayesian phase II platform design, the Multi-candidate Iterative Design with Adaptive Selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and “graduate” the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. PMID:27112322

  13. 25 CFR 519.1 - Designation of an agent by a tribe.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Designation of an agent by a tribe. 519.1 Section 519.1 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS SERVICE § 519.1 Designation of an agent by a tribe. By written notification to the Commission, a tribe shall designate an...

  14. 25 CFR 519.1 - Designation of an agent by a tribe.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Designation of an agent by a tribe. 519.1 Section 519.1 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS SERVICE § 519.1 Designation of an agent by a tribe. By written notification to the Commission, a tribe shall designate an...

  15. 25 CFR 519.1 - Designation of an agent by a tribe.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Designation of an agent by a tribe. 519.1 Section 519.1 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS SERVICE § 519.1 Designation of an agent by a tribe. By written notification to the Commission, a tribe shall designate an...

  16. 25 CFR 519.1 - Designation of an agent by a tribe.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Designation of an agent by a tribe. 519.1 Section 519.1 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS SERVICE § 519.1 Designation of an agent by a tribe. By written notification to the Commission, a tribe shall designate an...

  17. 25 CFR 519.1 - Designation of an agent by a tribe.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Designation of an agent by a tribe. 519.1 Section 519.1 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS SERVICE § 519.1 Designation of an agent by a tribe. By written notification to the Commission, a tribe shall designate an...

  18. Integrating the Engineering Curriculum through the Synthesis and Design Studio

    ERIC Educational Resources Information Center

    Kellam, Nadia; Walther, Joachim; Costantino, Tracie; Cramond, Bonnie

    2013-01-01

    Traditional curricular approaches within engineering education tend to be fragmented, with opportunities for content- and meta-level synthesis being mostly limited to freshman and senior year design courses. In this paper, we are proposing a curricular model, the Synthesis and Design Studio, to combat the tendency towards fragmented curricula. The…

  19. Rational Design, Development, and Stability Assessment of a Macrocyclic Four-Hydroxamate-Bearing Bifunctional Chelating Agent for 89 Zr.

    PubMed

    Seibold, Uwe; Wängler, Björn; Wängler, Carmen

    2017-09-21

    Zirconium-89 is a positron-emitting radionuclide of high interest for medical imaging applications with positron emission tomography (PET). For the introduction of this radiometal into biologically active targeting vectors, the chelating agent desferrioxamine B (DFO) is commonly applied. However, DFO is known to form 89 Zr complexes of limited in vivo stability. Herein we describe the rational design and chemical development of a new macrocyclic four-hydroxamate-bearing chelating agent-1,10,19,28-tetrahydroxy-1,5,10,14,19,23,28,32-octaazacyclohexatriacontan-2,6,11,15,20,24,29,33-octaone (CTH36)-for the stable complexation of Zr 4+ . For this purpose, we first performed computational studies to determine the optimal chelator geometry before we developed different synthesis pathways toward the target structures. The best results were obtained using an efficient solution-phase-based synthesis strategy toward the target chelating agent. To enable efficient and chemoselective conjugation to biomolecules, a tetrazine-modified variant of CTH36 was also developed. The excellent conjugation characteristics of the so-functionalized chelator were demonstrated on the example of the model peptide TCO-c(RGDfK). We determined the optimal 89 Zr radiolabeling parameters for CTH36 as well as its bioconjugate, and found that 89 Zr radiolabeling proceeds efficiently under very mild reaction conditions. Finally, we performed comparative complex stability tests for 89 Zr-CHT36-c(RGDfK) and 89 Zr-DFO-c(RGDfK), showing improved complex stability for the newly developed chelator CTH36. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin-avidin-specific binding.

    PubMed

    Liu, Yongjun; Wu, Xiaoyun; Sun, Xiaohe; Wang, Dan; Zhong, Ying; Jiang, Dandan; Wang, Tianqi; Yu, Dexin; Zhang, Na

    2017-01-01

    Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin-avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P <0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM -1 s -1 ) was observed compared to Magnevist ® (4.9 mM -1 s -1 ; P <0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor.

  1. Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding

    PubMed Central

    Liu, Yongjun; Wu, Xiaoyun; Sun, Xiaohe; Wang, Dan; Zhong, Ying; Jiang, Dandan; Wang, Tianqi; Yu, Dexin; Zhang, Na

    2017-01-01

    Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin–avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P<0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM−1 s−1) was observed compared to Magnevist® (4.9 mM−1 s−1; P<0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor. PMID:28765707

  2. MIDAS: a practical Bayesian design for platform trials with molecularly targeted agents.

    PubMed

    Yuan, Ying; Guo, Beibei; Munsell, Mark; Lu, Karen; Jazaeri, Amir

    2016-09-30

    Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time and thus not efficient for this task. We propose a Bayesian phase II platform design, the multi-candidate iterative design with adaptive selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and 'graduate' the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Effect of both protective and reducing agents in the synthesis of multicolor silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Rivero, Pedro Jose; Goicoechea, Javier; Urrutia, Aitor; Arregui, Francisco Javier

    2013-02-01

    In this paper, the influence of variable molar ratios between reducing and loading agents (1:100, 1:50, 1:20, 1:10, 1:5, 1:2, 1:1, 2:1) and between protective and loading agents (0.3:1, 0.75:1, 1.5:1, 3:1, 7.5:1, 30:1, 75:1) in the synthesis of silver nanoparticles by chemical reduction has been evaluated to obtain multicolor nanoparticles with a high stability in time. The protective agent poly(acrylic acid, sodium salt) (PAA) and reducing agent dimethylaminoborane (DMAB) play a key role in the formation of the resultant color. Evolution of the optical absorption bands of the silver nanoparticles as a function of PAA and DMAB molar ratios made it possible to confirm the presence of silver nanoparticles or clusters with a specific shape. The results reveal that a wide range of colors (violet, blue, green, brown, yellow, red, orange), sizes (from nanometer to micrometer), and shapes (cubic, rod, triangle, hexagonal, spherical) can be perfectly tuned by means of a fine control of the PAA and DMAB molar concentrations.

  4. Design, synthesis and structure-activity relationship evaluation of novel LpxC inhibitors as Gram-negative antibacterial agents.

    PubMed

    Ding, Shi; Dai, Rui-Yang; Wang, Wen-Ke; Cao, Qiao; Lan, Le-Fu; Zhou, Xian-Li; Yang, Yu-She

    2018-01-15

    LpxC inhibitors are new-type antibacterial agents developed in the last twenty years, mainly against Gram-negative bacteria infections. To develop novel LpxC inhibitors with good antibacterial activities and biological metabolism, we summarized the basic skeleton of reported LpxC inhibitors, designed and synthesized several series of compounds and tested their antibacterial activities against Escherichial coli and Pseudomonas aeruginosa in vitro. Structure-activity relationships have been discussed in this article. The metabolism stability of YDL-2, YDL-5, YDL-8, YDL-14, YDL-20-YDL-23 have been evaluated in liver microsomes, which indicated that the 2-amino isopropyl group may be a preferred structure than the 2-hydroxy ethyl group in the design of LpxC inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Microgravity isolation system design: A modern control synthesis framework

    NASA Technical Reports Server (NTRS)

    Hampton, R. D.; Knospe, C. R.; Allaire, P. E.; Grodsinsky, C. M.

    1994-01-01

    Manned orbiters will require active vibration isolation for acceleration-sensitive microgravity science experiments. Since umbilicals are highly desirable or even indispensable for many experiments, and since their presence greatly affects the complexity of the isolation problem, they should be considered in control synthesis. In this paper a general framework is presented for applying extended H2 synthesis methods to the three-dimensional microgravity isolation problem. The methodology integrates control and state frequency weighting and input and output disturbance accommodation techniques into the basic H2 synthesis approach. The various system models needed for design and analysis are also presented. The paper concludes with a discussion of a general design philosophy for the microgravity vibration isolation problem.

  6. Microgravity isolation system design: A modern control synthesis framework

    NASA Technical Reports Server (NTRS)

    Hampton, R. D.; Knospe, C. R.; Allaire, P. E.; Grodsinsky, C. M.

    1994-01-01

    Manned orbiters will require active vibration isolation for acceleration-sensitive microgravity science experiments. Since umbilicals are highly desirable or even indispensable for many experiments, and since their presence greatly affects the complexity of the isolation problem, they should be considered in control synthesis. A general framework is presented for applying extended H2 synthesis methods to the three-dimensional microgravity isolation problem. The methodology integrates control and state frequency weighting and input and output disturbance accommodation techniques into the basic H2 synthesis approach. The various system models needed for design and analysis are also presented. The paper concludes with a discussion of a general design philosophy for the microgravity vibration isolation problem.

  7. Design of Nanomaterial Synthesis by Aerosol Processes

    PubMed Central

    Buesser, Beat; Pratsinis, Sotiris E.

    2013-01-01

    Aerosol synthesis of materials is a vibrant field of particle technology and chemical reaction engineering. Examples include the manufacture of carbon blacks, fumed SiO2, pigmentary TiO2, ZnO vulcanizing catalysts, filamentary Ni, and optical fibers, materials that impact transportation, construction, pharmaceuticals, energy, and communications. Parallel to this, development of novel, scalable aerosol processes has enabled synthesis of new functional nanomaterials (e.g., catalysts, biomaterials, electroceramics) and devices (e.g., gas sensors). This review provides an access point for engineers to the multiscale design of aerosol reactors for the synthesis of nanomaterials using continuum, mesoscale, molecular dynamics, and quantum mechanics models spanning 10 and 15 orders of magnitude in length and time, respectively. Key design features are the rapid chemistry; the high particle concentrations but low volume fractions; the attainment of a self-preserving particle size distribution by coagulation; the ratio of the characteristic times of coagulation and sintering, which controls the extent of particle aggregation; and the narrowing of the aggregate primary particle size distribution by sintering. PMID:22468598

  8. Design of nanomaterial synthesis by aerosol processes.

    PubMed

    Buesser, Beat; Pratsinis, Sotiris E

    2012-01-01

    Aerosol synthesis of materials is a vibrant field of particle technology and chemical reaction engineering. Examples include the manufacture of carbon blacks, fumed SiO(2), pigmentary TiO(2), ZnO vulcanizing catalysts, filamentary Ni, and optical fibers, materials that impact transportation, construction, pharmaceuticals, energy, and communications. Parallel to this, development of novel, scalable aerosol processes has enabled synthesis of new functional nanomaterials (e.g., catalysts, biomaterials, electroceramics) and devices (e.g., gas sensors). This review provides an access point for engineers to the multiscale design of aerosol reactors for the synthesis of nanomaterials using continuum, mesoscale, molecular dynamics, and quantum mechanics models spanning 10 and 15 orders of magnitude in length and time, respectively. Key design features are the rapid chemistry; the high particle concentrations but low volume fractions; the attainment of a self-preserving particle size distribution by coagulation; the ratio of the characteristic times of coagulation and sintering, which controls the extent of particle aggregation; and the narrowing of the aggregate primary particle size distribution by sintering.

  9. General aviation design synthesis utilizing interactive computer graphics

    NASA Technical Reports Server (NTRS)

    Galloway, T. L.; Smith, M. R.

    1976-01-01

    Interactive computer graphics is a fast growing area of computer application, due to such factors as substantial cost reductions in hardware, general availability of software, and expanded data communication networks. In addition to allowing faster and more meaningful input/output, computer graphics permits the use of data in graphic form to carry out parametric studies for configuration selection and for assessing the impact of advanced technologies on general aviation designs. The incorporation of interactive computer graphics into a NASA developed general aviation synthesis program is described, and the potential uses of the synthesis program in preliminary design are demonstrated.

  10. Rational Design, Synthesis, and Biological Evaluation of Third Generation α-Noscapine Analogues as Potent Tubulin Binding Anti-Cancer Agents

    PubMed Central

    Manchukonda, Naresh Kumar; Naik, Pradeep Kumar; Santoshi, Seneha; Lopus, Manu; Joseph, Silja; Sridhar, Balasubramanian; Kantevari, Srinivas

    2013-01-01

    Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.252 to -5.402 kCal/mol) than the parent compound, noscapine (-5.505 kCal/mol) and its existing derivatives (-5.563 to -6.412 kCal/mol). Free energy (ΔG bind) calculations based on the linear interaction energy (LIE) empirical equation utilizing Surface Generalized Born (SGB) continuum solvent model predicted the tubulin-binding affinities for the derivatives 5a, 6a-j (ranging from -4.923 to -6.189 kCal/mol). Compound 6f showed highest binding affinity to tubulin (-6.189 kCal/mol). The experimental evaluation of these compounds corroborated with theoretical studies. N-(3-brormobenzyl) noscapine (6f) binds tubulin with highest binding affinity (KD, 38 ± 4.0 µM), which is ~ 4.0 times higher than that of the parent compound, noscapine (KD, 144 ± 1.0 µM) and is also more potent than that of the first generation clinical candidate EM011, 9-bromonoscapine (KD, 54 ± 9.1 µM). All these compounds exhibited substantial cytotoxicity toward cancer cells, with IC50 values ranging from 6.7 µM to 72.9 µM; compound 6f showed prominent anti-cancer efficacy with IC50 values ranging from 6.7 µM to 26.9 µM in cancer cells of different tissues of origin. These compounds perturbed DNA synthesis, delayed the cell cycle progression at G2/M phase, and induced apoptotic cell death in cancer cells. Collectively, the study reported here identified potent, third generation noscapinoids as new anti-cancer agents. PMID:24205049

  11. Design, Synthesis and in vitro Biochemical Activity of Novel Amino Acid Sulfonohydrazide Inhibitors of MurC.

    PubMed

    Frlan, Rok; Kovač, Andreja; Blanot, Didier; Gobec, Stanislav; Pečar, Slavko; Obreza, Aleš

    2011-06-01

    Mur ligases are essential enzymes involved in the cytoplasmic steps of peptidoglycan synthesis which remain attractive, yet unexploited targets. In order to develop new antibacterial agents, we have designed a series of new MurC and MurD inhibitors bearing amino acid sulfonohydrazide moiety. The L-Leu series of this class displayed the highest enzyme inhibition with IC50 in the concentration range between 100 and 500 µM, with L-Thr, L-Pro and L-Ala derivatives being inactive. The most promising compound of the series also expressed weak antibacterial activity against S. aureus with MIC = 128 µg/mL.

  12. Multi-Agent Design and Implementation for an Online Peer Help System

    ERIC Educational Resources Information Center

    Meng, Anbo

    2014-01-01

    With the rapid advance of e-learning, the online peer help is playing increasingly important role. This paper explores the application of MAS to an online peer help system (MAPS). In the design phase, the architecture of MAPS is proposed, which consists of a set of agents including the personal agent, the course agent, the diagnosis agent, the DF…

  13. Evaluation of Market Design Agents: The Mertacor Perspective

    NASA Astrophysics Data System (ADS)

    Stavrogiannis, Lampros C.; Mitkas, Pericles A.

    The annual Trading Agent Competition for Market Design, CAT, provides a testbed to study the mechanisms that modern stock exchanges use in their effort to attract potential traders while maximizing their profit. This paper presents an evaluation of the agents that participated in the 2008 competition. The evaluation is based on the analysis of the CAT finals as well as on the results obtained from post-tournament experiments. We present Mertacor, our entrant for 2008, and compare it with the other available agents. In addition, we introduce a simple yet effective way of computing the global competitive equilibrium that Mertacor utilizes and discuss its importance for the game.

  14. Virtual odors to transmit emotions in virtual agents

    NASA Astrophysics Data System (ADS)

    Delgado-Mata, Carlos; Aylett, Ruth

    2003-04-01

    In this paper we describe an emotional-behvioral architecture. The emotional engine sits at a higher layer than the behavior system, and can alter behavior patterns, the engine is designed to simulate Emotionally-Intelligent Agents in a Virtual Environment, where each agent senses its own emotions, and other creature emotions through a virtual smell sensor; senses obstacles and other moving creatures in the environment and reacts to them. The architecture consists of an emotion engine, behavior synthesis system, a motor layer and a library of sensors.

  15. Green chemistry for nanoparticle synthesis.

    PubMed

    Duan, Haohong; Wang, Dingsheng; Li, Yadong

    2015-08-21

    The application of the twelve principles of green chemistry in nanoparticle synthesis is a relatively new emerging issue concerning the sustainability. This field has received great attention in recent years due to its capability to design alternative, safer, energy efficient, and less toxic routes towards synthesis. These routes have been associated with the rational utilization of various substances in the nanoparticle preparations and synthetic methods, which have been broadly discussed in this tutorial review. This article is not meant to provide an exhaustive overview of green synthesis of nanoparticles, but to present several pivotal aspects of synthesis with environmental concerns, involving the selection and evaluation of nontoxic capping and reducing agents, the choice of innocuous solvents and the development of energy-efficient synthetic methods.

  16. Novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents: Design, synthesis and biological evaluation.

    PubMed

    Liu, Han-Bo; Gao, Wei-Wei; Tangadanchu, Vijai Kumar Reddy; Zhou, Cheng-He; Geng, Rong-Xia

    2018-01-01

    A series of novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents were designed, synthesized and characterized by IR, NMR and HRMS spectra. The biological evaluation in vitro revealed that some of the target compounds exerted good antibacterial and antifungal activity in comparison with the reference drugs. Noticeably, compound 7d could effectively inhibit the growth of A. flavus, E. coli DH52 and MRSA with MIC values of 1, 1 and 8 μg/mL, respectively. Further studies revealed that pyrimidine derivative 7d could exhibit bactericidal mode of action against both Gram positive (S. aureus and MRSA) and Gram negative (P. aeruginosa) bacteria. The active molecule 7d showed low cell toxicity and did not obviously trigger the development of resistance in bacteria even after 16 passages. Furthermore, compound 7d was able to beneficially regulate reactive oxygen species (ROS) generation for an excellent safety profile. Molecular docking study revealed that compound 7d could bind with DNA gyrase by the formation of hydrogen bonds. The preliminary exploration for antimicrobial mechanism disclosed that compound 7d could effectively intercalate into calf thymus DNA to form a steady supramolecular complex, which might further block DNA replication to exert the powerful bioactivities. The binding investigation of compound 7d with human serum albumins (HSA) revealed that this molecule could be effectively transported by HSA. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Function-Oriented Synthesis: How to Design Simplified Analogues of Antibacterial Nucleoside Natural Products?

    PubMed

    Ichikawa, Satoshi

    2016-06-01

    It is important to pursue function-oriented synthesis (FOS), a strategy for the design of less structurally complex targets with comparable or superior activity that can be made in a practical manner, because compared to synthetic drugs, many biologically relevant natural products possess large and complex chemical structures that may restrict chemical modifications in a structure-activity relationship study. In this account, we describe recent efforts to simplify complex nucleoside natural products including caprazamycins. Considering the structure-activity relationship study with several truncated analogues, three types of simplified derivatives, namely, oxazolidine, isoxazolidine, and lactam-fused isoxazolidine-containing uridine derivatives, were designed and efficiently synthesized. These simplified derivatives have exhibited promising antibacterial activities. A significant feature of our studies is the rational and drastic simplification of the molecular architecture of caprazamycins. This study provides a novel strategy for the development of a new type of antibacterial agent effective against drug-resistant bacteria. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Design and Solution-Phase Synthesis of Membrane-Targeting Lipopeptides with Selective Antibacterial Activity.

    PubMed

    Konai, Mohini M; Adhikary, Utsarga; Haldar, Jayanta

    2017-09-18

    Designing selective antibacterial molecules remains an unmet goal in the field of membrane-targeting agents. Herein, we report the rational design and synthesis of a new class of lipopeptides, which possess highly selective bacterial killing over mammalian cells. The selective interaction with bacterial over mammalian membranes was established through various spectroscopic, as well as microscopic experiments, including biophysical studies with the model membranes. A detailed antibacterial structure-activity relationship was delineated after preparing a series of molecules consisting of the peptide moieties with varied sequence of amino acids, such as d-phenylalanine, d-leucine, and d-lysine. Antibacterial activity was found to vary with the nature and positioning of hydrophobicity in the molecules, as well as number of positive charges. Optimized lipopeptide 9 did not show any hemolytic activity even at 1000 μg mL -1 and displayed >200-fold and >100-fold selectivity towards S. aureus and E. coli, respectively. More importantly, compound 9 was found to display good antibacterial activity (MIC 6.3-12.5 μg mL -1 ) against the five top most critical bacteria according to World Health Organization (WHO) priority pathogens list. Therefore, the results suggested that this new class of lipopeptides bear real promises for the development as future antibacterial agents. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent

    PubMed Central

    Heinrich, Tobias K.; Gottumukkala, Vijay; Snay, Erin; Dunning, Patricia; Fahey, Frederic H; Treves, S. Ted; Packard, Alan B.

    2009-01-01

    There is considerable interest in developing an 18F-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with 99mTc-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an 18F-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like 99mTc-MIBI, rhodamine dyes are known to accumulate in the myocardium and are substrates for Pgp, the protein implicated in MDR1 multidrug resistance. As the first step in determining whether 18F-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the 18F-labeled compounds so that they could be evaluated in vivo. Rhodamine B was chosen as the prototype compound for development of the synthesis because the ethyl substituents on the amine moieties of rhodamine B protect them from side reactions, thus eliminating the need to include (and subsequently remove) protecting groups. The 2′-[18F]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [18F]fluoroethyltosylate in acetonitrile at 165°C for 30 min.using [18F]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K2CO3, and [18F]NaF in acetonitrile for 10 min. at 90°C. The product was purified by semi-preparative HPLC to produce the 2′-[18F]-fluoroethylester in >97% radiochemical purity with a specific activity of 1.3 GBq/μmol, an isolated decay corrected yield of 35%, and a total synthesis time of 90 min. PMID:19783150

  20. I. Development of Metal-Mediated SPOT-Synthesis Methods for the Efficient Construction of Small-Molecule Macroarrays. II. Design and Synthesis of Novel Bacterial Biofilm Inhibitors

    NASA Astrophysics Data System (ADS)

    Frei, Reto

    I. The use of small molecule probes to explore biological phenomena has become a valuable tool in chemical biology. As a result, methods that permit the rapid synthesis and biological evaluation of such compounds are highly sought-after. The small molecule macroarray represents one such approach for the synthesis and identification of novel bioactive agents. Macroarrays are readily constructed via the SPOT-synthesis technique on planar cellulose membranes, yielding spatially addressed libraries of ˜10-1000 unique compounds. We sought to expand the arsenal of chemical reactions compatible with this solid-phase platform, and developed highly efficient SPOT-synthesis protocols for the Mizoroki-Heck, Suzuki-Miyaura, and copper-catalyzed azide-alkyne cycloaddition reaction. We demonstrated that these metal-mediated reactions can be implemented, either individually or sequentially, for the efficient construction of small molecules in high purity on rapid time scales. Utilizing these powerful C-C and C-N bond forming coupling reactions, we constructed a series of macroarrays based on novel stilbene, phenyl-naphthalene, and triazole scaliblds. Subsequent biological testing of the stilbene and phenyl-naphthalene libraries revealed several potent antagonists and agonists, respectively, of the quorum sensing (QS) receptor LuxR in Vibrio fischeri. II. Bacteria living within biofilms are notorious for their resistance to known antibiotic agents, and constitute a major human health threat. Methods to attenuate biofilm growth would have a significant impact on the management of bacterial infections. Despite intense research efforts, small molecules capable of either inhibiting or dispersing biolilms remain scarce. We utilized natural products with purported anti-biofilm or QS inhibitory activity as sources of structural insight to guide the synthesis of novel biofilm modulators with improved activities. These studies revealed 2-aminobenzimidazole derivatives as highly potent

  1. Enzymatic Synthesis of Lignin-Based Concrete Dispersing Agents.

    PubMed

    Jankowska, Dagmara; Heck, Tobias; Schubert, Mark; Yerlikaya, Alpaslan; Weymuth, Christophe; Rentsch, Daniel; Schober, Irene; Richter, Michael

    2018-03-15

    Lignin is the most abundant aromatic biopolymer, functioning as an integral component of woody materials. In its unmodified form it shows limited water solubility and is relatively unreactive, so biotechnological lignin valorisation for high-performance applications is greatly underexploited. Lignin can be obtained from the pulp and paper industry as a by-product. To expand its application, a new synthesis route to new dispersing agents for use as concrete additives was developed. The route is based on lignin functionalisation by enzymatic transformation. Screening of lignin-modifying systems resulted in functionalised lignin polymers with improved solubility in aqueous systems. Through grafting of sulfanilic acid or p-aminobenzoic acid by fungal laccases, lignin became soluble in water at pH≤4 or pH≤7, respectively. Products were analysed and evaluated in miniaturised application tests in cement paste and mortar. Their dispersing properties match the performance criteria of commercially available lignosulfonates. The study provides examples of new perspectives for the use of lignin. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. A two-dimensional biased coin design for dual-agent dose-finding trials.

    PubMed

    Sun, Zhichao; Braun, Thomas M

    2015-12-01

    Given the limited efficacy observed with single agents, there is growing interest in Phase I clinical trial designs that allow for identification of the maximum tolerated combination of two agents. Existing parametric designs may suffer from over- or under-parameterization. Thus, we have designed a nonparametric approach that can be easily understood and implemented for combination trials. We propose a two-stage adaptive biased coin design that extends existing methods for single-agent trials to dual-agent dose-finding trials. The basic idea of our design is to divide the entire trial into two stages and apply the biased coin design, with modification, in each stage. We compare the operating characteristics of our design to four competing parametric approaches via simulation in several numerical examples. Under all simulation scenarios we have examined, our method performs well in terms of identification of the maximum tolerated combination and allocation of patients relative to the performance of its competitors. In our design, stopping rule criteria and the distribution of the total sample size among the two stages are context-dependent, and both need careful consideration before adopting our design in practice. Efficacy is not a part of the dose-assignment algorithm, nor used to define the maximum tolerated combination. Our design inherits the favorable statistical properties of the biased coin design, is competitive with existing designs, and promotes patient safety by limiting patient exposure to toxic combinations whenever possible. © The Author(s) 2015.

  3. New p-methylsulfonamido phenylethylamine analogues as class III antiarrhythmic agents: design, synthesis, biological assay, and 3D-QSAR analysis.

    PubMed

    Liu, Hong; Ji, Ming; Luo, Xiaomin; Shen, Jianhua; Huang, Xiaoqin; Hua, Weiyi; Jiang, Hualiang; Chen, Kaixian

    2002-07-04

    Class III antiarrhythmic agents selectively delay the effective refractory period (ERP) and increase the transmembrane action potential duration (APD). Using dofetilide (2) as a template of class III antiarrhythmic agents, we designed and synthesized 16 methylsulfonamido phenylethylamine analogues (4a-d and 5a-l). Pharmacological assay indicated that all of these compounds showed activity for increasing the ERP in isolated animal atrium; among them, the effective concentration of compound 4a is 1.6 x 10(-8) mol/L in increasing ERP by 10 ms, slightly less potent than that of 2, 1.1 x 10(-8) mol/L. Compound 4a also produced a slightly lower change in ERP at 10(-5) M, DeltaERP% = 17.5% (DeltaERP% = 24.0% for dofetilide). On the basis of this bioassay result, these 16 compounds together with dofetilide were investigated by the three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques of comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and the hologram QSAR (HQSAR). The 3D-QSAR models were tested with another 11 compounds (4e-h and 5m-s) that we synthesized later. Results revealed that the CoMFA, CoMSIA, and HQSAR predicted activities for the 11 newly synthesized compounds that have a good correlation with their experimental value, r(2) = 0.943, 0.891, and 0.809 for the three QSAR models, respectively. This indicates that the 3D-QSAR models proved a good predictive ability and could describe the steric, electrostatic, and hydrophobic requirements for recognition forces of the receptor site. On the basis of these results, we designed and synthesized another eight new analogues of methanesulfonamido phenylethyamine (6a-h) according to the clues provided by the 3D-QSAR analyses. Pharmacological assay indicated that the effective concentrations of delaying the ERP by 10 ms of these newly designed compounds correlated well with the 3D-QSAR predicted values. It is remarkable that the percent

  4. Robust parameter design for automatically controlled systems and nanostructure synthesis

    NASA Astrophysics Data System (ADS)

    Dasgupta, Tirthankar

    2007-12-01

    This research focuses on developing comprehensive frameworks for developing robust parameter design methodology for dynamic systems with automatic control and for synthesis of nanostructures. In many automatically controlled dynamic processes, the optimal feedback control law depends on the parameter design solution and vice versa and therefore an integrated approach is necessary. A parameter design methodology in the presence of feedback control is developed for processes of long duration under the assumption that experimental noise factors are uncorrelated over time. Systems that follow a pure-gain dynamic model are considered and the best proportional-integral and minimum mean squared error control strategies are developed by using robust parameter design. The proposed method is illustrated using a simulated example and a case study in a urea packing plant. This idea is also extended to cases with on-line noise factors. The possibility of integrating feedforward control with a minimum mean squared error feedback control scheme is explored. To meet the needs of large scale synthesis of nanostructures, it is critical to systematically find experimental conditions under which the desired nanostructures are synthesized reproducibly, at large quantity and with controlled morphology. The first part of the research in this area focuses on modeling and optimization of existing experimental data. Through a rigorous statistical analysis of experimental data, models linking the probabilities of obtaining specific morphologies to the process variables are developed. A new iterative algorithm for fitting a Multinomial GLM is proposed and used. The optimum process conditions, which maximize the above probabilities and make the synthesis process less sensitive to variations of process variables around set values, are derived from the fitted models using Monte-Carlo simulations. The second part of the research deals with development of an experimental design methodology, tailor

  5. Rapid synthesis of gold and silver nanoparticles using tryptone as a reducing and capping agent

    NASA Astrophysics Data System (ADS)

    Mehta, Sourabh M.; Sequeira, Marilyn P.; Muthurajana, Harries; D'Souza, Jacinta S.

    2018-02-01

    Due to its eco-friendliness, recent times have seen an immense interest in the green synthesis of metallic nanoparticles. We present here, a protocol for the rapid and cheap synthesis of Au and Ag nanoparticles (NPs) using 1 mg/ml tryptone (trypsinized casein) as a reducing and capping agent. These nanoparticles are spherical, 10 nm in diameter and relatively monodispersed. The atoms of these NPs are arranged in face-centered cubic fashion. Further, when tested for their cytotoxic property against HeLa and VERO cell lines, gold nanoparticles were more lethal than silver nanoparticles, with a more or less similar trend observed against both Gram-positive and Gram-negative bacteria. On the other hand, the NPs were least cytotoxic against a unicellular alga, Chlamydomonas reinhardtii implying their eco-friendly property.

  6. Synthesis and evaluation of novel caged DNA alkylating agents bearing 3,4-epoxypiperidine structure.

    PubMed

    Kawada, Yuji; Kodama, Tetsuya; Miyashita, Kazuyuki; Imanishi, Takeshi; Obika, Satoshi

    2012-07-14

    Previously, we reported that the 3,4-epoxypiperidine structure, whose design was based on the active site of DNA alkylating antitumor antibiotics, azinomycins A and B, possesses prominent DNA cleavage activity. In this report, novel caged DNA alkylating agents, which were designed to be activated by UV irradiation, were synthesized by the introduction of four photo-labile protecting groups to a 3,4-epoxypiperidine derivative. The DNA cleavage activity and cytotoxicity of the caged DNA alkylating agents were examined under UV irradiation. Four caged DNA alkylating agents showed various degrees of bioactivity depending on the photosensitivity of the protecting groups.

  7. Conformation-Based Design and Synthesis of Apratoxin A Mimetics Modified at the α,β-Unsaturated Thiazoline Moiety.

    PubMed

    Onda, Yuichi; Masuda, Yuichi; Yoshida, Masahito; Doi, Takayuki

    2017-08-10

    We have demonstrated design, synthesis, and biological evaluation of apratoxin A mimetics. In the first generation, the moCys moiety was replaced with seven simple amino acids as their 3D structures can be similar to that of apratoxin A. Apratoxins M1-M7 were synthesized using solid-phase peptide synthesis and solution-phase macrolactamization. Apratoxin M7, which contains a piperidinecarboxylic acid moiety, exhibited potent cytotoxicity against HCT-116 cells. In the second generation, substitution of each amino acid residue in the tripeptide Tyr(Me)-MeAla-MeIle moiety in apratoxin M7 led to the development of the highly potent apratoxin M16 possessing biphenylalanine (Bph) instead of Tyr(Me), which exhibited an IC 50 value of 1.1 nM against HCT-116 cells. Moreover, compared to apratoxin A, apratoxin M16 exhibited a similarly high level of growth inhibitory activity against various cancer cell lines. The results indicate that apratoxin M16 could be a potential candidate as an anticancer agent.

  8. Design and Synthesis of Biaryl DNA-Encoded Libraries.

    PubMed

    Ding, Yun; Franklin, G Joseph; DeLorey, Jennifer L; Centrella, Paolo A; Mataruse, Sibongile; Clark, Matthew A; Skinner, Steven R; Belyanskaya, Svetlana

    2016-10-10

    DNA-encoded library technology (ELT) is a powerful tool for the discovery of new small-molecule ligands to various protein targets. Here we report the design and synthesis of biaryl DNA-encoded libraries based on the scaffold of 5-formyl 3-iodobenzoic acid. Three reactions on DNA template, acylation, Suzuki-Miyaura coupling and reductive amination, were applied in the library synthesis. The three cycle library of 3.5 million diversity has delivered potent hits for phosphoinositide 3-kinase α (PI3Kα).

  9. Process optimization using combinatorial design principles: parallel synthesis and design of experiment methods.

    PubMed

    Gooding, Owen W

    2004-06-01

    The use of parallel synthesis techniques with statistical design of experiment (DoE) methods is a powerful combination for the optimization of chemical processes. Advances in parallel synthesis equipment and easy to use software for statistical DoE have fueled a growing acceptance of these techniques in the pharmaceutical industry. As drug candidate structures become more complex at the same time that development timelines are compressed, these enabling technologies promise to become more important in the future.

  10. In-Silico Design, Synthesis and Evaluation of a Nanostructured Hydrogel as a Dimethoate Removal Agent.

    PubMed

    Avila-Salas, Fabian; Marican, Adolfo; Villaseñor, Jorge; Arenas-Salinas, Mauricio; Argandoña, Yerko; Caballero, Julio; Durán-Lara, Esteban F

    2018-01-04

    This study describes the in-silico design, synthesis, and evaluation of a cross-linked PVA hydrogel (CLPH) for the absorption of organophosphorus pesticide dimethoate from aqueous solutions. The crosslinking effectiveness of 14 dicarboxilic acids was evaluated through in-silico studies using semiempirical quantum mechanical calculations. According to the theoretical studies, the nanopore of PVA cross-linked with malic acid (CLPH-MA) showed the best interaction energy with dimethoate. Later, using all-atom molecular dynamics simulations, three hydrogels with different proportions of PVA:MA (10:2, 10:4, and 10:6) were used to evaluate their interactions with dimethoate. These results showed that the suitable crosslinking degree for improving the affinity for the pesticide was with 20% ( W %) of the cross-linker. In the experimental absorption study, the synthesized CLPH-MA20 recovered 100% of dimethoate from aqueous solutions. Therefore, the theoretical data were correlated with the experimental studies. Surface morphology of CLPH-MA20 by Scanning Electron Microscopy (SEM) was analyzed. In conclusion, the ability of CLPH-MA20 to remove dimethoate could be used as a technological alternative for the treatment of contaminated water.

  11. In-Silico Design, Synthesis and Evaluation of a Nanostructured Hydrogel as a Dimethoate Removal Agent

    PubMed Central

    Avila-Salas, Fabian; Marican, Adolfo; Villaseñor, Jorge; Argandoña, Yerko

    2018-01-01

    This study describes the in-silico design, synthesis, and evaluation of a cross-linked PVA hydrogel (CLPH) for the absorption of organophosphorus pesticide dimethoate from aqueous solutions. The crosslinking effectiveness of 14 dicarboxilic acids was evaluated through in-silico studies using semiempirical quantum mechanical calculations. According to the theoretical studies, the nanopore of PVA cross-linked with malic acid (CLPH-MA) showed the best interaction energy with dimethoate. Later, using all-atom molecular dynamics simulations, three hydrogels with different proportions of PVA:MA (10:2, 10:4, and 10:6) were used to evaluate their interactions with dimethoate. These results showed that the suitable crosslinking degree for improving the affinity for the pesticide was with 20% (W%) of the cross-linker. In the experimental absorption study, the synthesized CLPH-MA20 recovered 100% of dimethoate from aqueous solutions. Therefore, the theoretical data were correlated with the experimental studies. Surface morphology of CLPH-MA20 by Scanning Electron Microscopy (SEM) was analyzed. In conclusion, the ability of CLPH-MA20 to remove dimethoate could be used as a technological alternative for the treatment of contaminated water. PMID:29300312

  12. Hydroxypyridonate chelating agents and synthesis thereof

    DOEpatents

    Raymond, K.N.; Scarrow, R.C.; White, D.L.

    1985-11-12

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.

  13. Expert System for Automated Design Synthesis

    NASA Technical Reports Server (NTRS)

    Rogers, James L., Jr.; Barthelemy, Jean-Francois M.

    1987-01-01

    Expert-system computer program EXADS developed to aid users of Automated Design Synthesis (ADS) general-purpose optimization program. EXADS aids engineer in determining best combination based on knowledge of specific problem and expert knowledge stored in knowledge base. Available in two interactive machine versions. IBM PC version (LAR-13687) written in IQ-LISP. DEC VAX version (LAR-13688) written in Franz-LISP.

  14. Designing Agent Collectives For Systems With Markovian Dynamics

    NASA Technical Reports Server (NTRS)

    Wolpert, David H.; Lawson, John W.

    2004-01-01

    The Collective Intelligence (COIN) framework concerns the design of collectives of agents so that as those agents strive to maximize their individual utility functions, their interaction causes a provided world utility function concerning the entire collective to be also maximized. Here we show how to extend that framework to scenarios having Markovian dynamics when no re-evolution of the system from counter-factual initial conditions (an often expensive calculation) is permitted. Our approach transforms the (time-extended) argument of each agent's utility function before evaluating that function. This transformation has benefits in scenarios not involving Markovian dynamics of an agent's utility function are observable. We investigate this transformation in simulations involving both hear and quadratic (nonlinear) dynamics. In addition, we find that a certain subset of these transformations, which result in utilities that have low opacity (analogous to having high signal to noise) but are not factored (analogous to not being incentive compatible), reliably improve performance over that arising with factored utilities. We also present a Taylor Series method for the fully general nonlinear case.

  15. Synthesis and biological evaluation of pyrazolylthiazole carboxylic acids as potent anti-inflammatory-antimicrobial agents.

    PubMed

    Khloya, Poonam; Kumar, Satish; Kaushik, Pawan; Surain, Parveen; Kaushik, Dhirender; Sharma, Pawan K

    2015-03-15

    Current Letter presents design, synthesis and biological evaluation of a novel series of pyrazolylthiazole carboxylates 1a-1p and corresponding acid derivatives 2a-2p. All 32 novel compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema method as well as for in vitro antimicrobial activity. All the tested compounds exhibited excellent AI activity profile. Three compounds 1p (R=Cl, R(1)=Cl), 2c (R=H, R(1)=F) and 2n (R=Cl, R(1)=OCH3) were identified as potent anti-inflammatory agents exhibiting edema inhibition of 93.06-89.59% which is comparable to the reference drug indomethacin (91.32%) after 3h of carrageenan injection while most of the other compounds displayed inhibition ⩾80%. In addition, pyrazolylthiazole carboxylic acids (2a-2p) also showed good antimicrobial profile. Compound 2h (R=OCH3, R(1)=Cl) showed excellent antimicrobial activity (MIC 6.25μg/mL) against both Gram positive bacteria comparable with the reference drug ciprofloxacin (MIC 6.25μg/mL). Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Green Synthesis of Ag, Cu and AgCu Nanoparticles using Palm Leaves Extract as the Reducing and Stabilizing Agents

    NASA Astrophysics Data System (ADS)

    Mohamad, N. A. N.; Arham, N. A.; Junaidah, J.; Hadi, A.; Idris, S. A.

    2018-05-01

    This paper reports the green synthesis of Ag, Cu and AgCu nanoparticles at room temperature using palm leaves extract. The purpose of this study is to eliminate the use of chemicals in the synthesis of nanoparticles and evaluate the efficiency of the palm leaves extract as the reducing and stabilizing agents. The palm leaves extract was added to metal salt solution and continuously stirred until reaction completed. The produced nanoparticles were analyzed using atomic absorption spectroscopy (AAS), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The analyses revealed that palm leaves extract has efficiently reduced the silver ions, but not the copper ions. During synthesis of AgCu nanoparticles, simultaneous reduction was occurred leading to formation of alloyed nanoparticles. Biomolecules from the palm leaves extract adsorbed on the surface of nanoparticles forming a capping layer thus stabilized the nanoparticles. The produced Ag and Cu nanoparticles were predominantly spherical with the particle size of Cu nanoparticles were larger than Ag nanoparticles. The AgCu nanoparticles closely resembled the Ag nanoparticles due to high Ag content with average size of 13nm. Therefore, palm leaves extract has a potential to be a good reducing and stabilizing agents.

  17. Melanoma-targeted delivery system (part 1): design, synthesis and evaluation of releasable disulfide drug by glutathione.

    PubMed

    El Aissi, Radhia; Chezal, Jean-Michel; Tarrit, Sébastien; Chavignon, Olivier; Moreau, Emmanuel

    2015-08-28

    Here we describe the design and synthesis of a prodrug developed for pigmented melanoma therapy, consisting of a Melanin-Targeting Probe (MTP) conjugated to 5-iodo-2'-deoxyuridine (IUdR) with a reduction-sensitive pre-determined breaking point. Compared with the non-cleavable conjugate (17b), prodrug (17a) bearing a self-immolative disulfide linker achieved complete release of IUdR within 20 min in the presence of reducing agents such as DTT or glutathione. Analytical results also showed that prodrug (17a) was more sensitive than parent non-cleavable conjugate (17b) for a concentration range of glutathione similar to that found in the intracellular compartment of tumours. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  18. Design, Sustainable Synthesis, and Programmed Reactions of Templated N-Heteroaryl-Fused Vinyl Sultams.

    PubMed

    Laha, Joydev K; Sharma, Shubhra; Kirar, Seema; Banerjee, Uttam C

    2017-09-15

    A de novo design and synthesis of N-heteroaryl-fused vinyl sultams as templates for programming chemical reactions on vinyl sultam periphery or (hetero)aryl ring is described. The key features include rational designing and sustainable synthesis of the template, customized reactions of vinyl sultams at C═C bond or involving N-S bond cleavage, and reactions on the periphery of the heteroaryl ring for late-stage diversification. The simple, easy access to the template coupled with opportunities for the synthesis of diversely functionalized heterocyles from a single template constitutes a rare study in contemporary organic synthesis.

  19. Convergent and sequential synthesis designs: implications for conducting and reporting systematic reviews of qualitative and quantitative evidence.

    PubMed

    Hong, Quan Nha; Pluye, Pierre; Bujold, Mathieu; Wassef, Maggy

    2017-03-23

    Systematic reviews of qualitative and quantitative evidence can provide a rich understanding of complex phenomena. This type of review is increasingly popular, has been used to provide a landscape of existing knowledge, and addresses the types of questions not usually covered in reviews relying solely on either quantitative or qualitative evidence. Although several typologies of synthesis designs have been developed, none have been tested on a large sample of reviews. The aim of this review of reviews was to identify and develop a typology of synthesis designs and methods that have been used and to propose strategies for synthesizing qualitative and quantitative evidence. A review of systematic reviews combining qualitative and quantitative evidence was performed. Six databases were searched from inception to December 2014. Reviews were included if they were systematic reviews combining qualitative and quantitative evidence. The included reviews were analyzed according to three concepts of synthesis processes: (a) synthesis methods, (b) sequence of data synthesis, and (c) integration of data and synthesis results. A total of 459 reviews were included. The analysis of this literature highlighted a lack of transparency in reporting how evidence was synthesized and a lack of consistency in the terminology used. Two main types of synthesis designs were identified: convergent and sequential synthesis designs. Within the convergent synthesis design, three subtypes were found: (a) data-based convergent synthesis design, where qualitative and quantitative evidence is analyzed together using the same synthesis method, (b) results-based convergent synthesis design, where qualitative and quantitative evidence is analyzed separately using different synthesis methods and results of both syntheses are integrated during a final synthesis, and (c) parallel-results convergent synthesis design consisting of independent syntheses of qualitative and quantitative evidence and an

  20. Design, synthesis, biological assessment and molecular docking studies of new 2-aminoimidazole-quinoxaline hybrids as potential anticancer agents

    NASA Astrophysics Data System (ADS)

    Ghanbarimasir, Zahra; Bekhradnia, Ahmadreza; Morteza-Semnani, Katayoun; Rafiei, Alireza; Razzaghi-Asl, Nima; Kardan, Mostafa

    2018-04-01

    In a search for novel antiproliferative agents, a series of quinoxaline derivatives containing 2-aminoimidazole (8a-8x) were designed and synthesized. The structures of synthesized compounds were confirmed by IR, 1H NMR, 13C NMR, Mass Spectroscopy and analyzed using HSQC, COSY, ROESY, HMBC techniques. The anticancer activity of all derivatives were evaluated for colon cancer and breast cancer cell lines by the MTT assay and acridine orange/ethidium bromide double staining method. The anti-cancer effect in human colon cancer (HCT-116) and breast cancer (MCF-7) cell lines exhibited that compounds 8a, 8s, 8t, 8w, 8x appeared as potent antiproliferative agents and especially inhibited the human colon cancer cell proliferation with percentage of inhibition by over 50%. The most active compound was (E)-4-phenyl-1-((quinoxalin-2-ylmethylene)amino)-1H-imidazol-2-amine (8a) with the highest inhibition for MCF-7 (83.3%) and HCT-116 (70%) cell lines after 48 and 24 h, respectively. Molecular docking studies of these derivatives within c-kit active site as a validated target might be suggested them as appropriate candidates for further efforts toward more potent anticancer compounds.

  1. DNA-Encoded Solid-Phase Synthesis: Encoding Language Design and Complex Oligomer Library Synthesis.

    PubMed

    MacConnell, Andrew B; McEnaney, Patrick J; Cavett, Valerie J; Paegel, Brian M

    2015-09-14

    The promise of exploiting combinatorial synthesis for small molecule discovery remains unfulfilled due primarily to the "structure elucidation problem": the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces mass redundancy and diverse scaffolds yield uninterpretable MS fragmentation. Here we present DNA-encoded solid-phase synthesis (DESPS), comprising parallel compound synthesis in organic solvent and aqueous enzymatic ligation of unprotected encoding dsDNA oligonucleotides. Computational encoding language design yielded 148 thermodynamically optimized sequences with Hamming string distance ≥ 3 and total read length <100 bases for facile sequencing. Ligation is efficient (70% yield), specific, and directional over 6 encoding positions. A series of isomers served as a testbed for DESPS's utility in split-and-pool diversification. Single-bead quantitative PCR detected 9 × 10(4) molecules/bead and sequencing allowed for elucidation of each compound's synthetic history. We applied DESPS to the combinatorial synthesis of a 75,645-member OBOC library containing scaffold, stereochemical and regiochemical diversity using mixed-scale resin (160-μm quality control beads and 10-μm screening beads). Tandem DNA sequencing/MALDI-TOF MS analysis of 19 quality control beads showed excellent agreement (<1 ppt) between DNA sequence-predicted mass and the observed mass. DESPS synergistically unites the advantages of solid-phase synthesis and DNA encoding, enabling single-bead structural elucidation of complex compounds and synthesis using reactions normally considered incompatible with unprotected DNA. The widespread availability of inexpensive oligonucleotide synthesis, enzymes, DNA sequencing, and PCR

  2. 37 CFR 201.38 - Designation of agent to receive notification of claimed infringement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., including a specific number and street name or rural route, of the agent designated to receive notification... it is the only address that can be used in that geographic location; (5) The telephone number, facsimile number, and electronic mail address of the agent designated to receive notification of claimed...

  3. 37 CFR 201.38 - Designation of agent to receive notification of claimed infringement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., including a specific number and street name or rural route, of the agent designated to receive notification... it is the only address that can be used in that geographic location; (5) The telephone number, facsimile number, and electronic mail address of the agent designated to receive notification of claimed...

  4. 37 CFR 201.38 - Designation of agent to receive notification of claimed infringement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., including a specific number and street name or rural route, of the agent designated to receive notification... it is the only address that can be used in that geographic location; (5) The telephone number, facsimile number, and electronic mail address of the agent designated to receive notification of claimed...

  5. 37 CFR 201.38 - Designation of agent to receive notification of claimed infringement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., including a specific number and street name or rural route, of the agent designated to receive notification... it is the only address that can be used in that geographic location; (5) The telephone number, facsimile number, and electronic mail address of the agent designated to receive notification of claimed...

  6. Red tea leaves infusion as a reducing and stabilizing agent in silver nanoparticles synthesis

    NASA Astrophysics Data System (ADS)

    Pluta, K.; Tryba, A. M.; Malina, D.; Sobczak-Kupiec, A.

    2017-12-01

    Due to the unique properties of silver nanoparticles there is growing interest in their applications. Current trends in nanotechnology are focused on developing a new technique to synthesize nanoparticles using biological methods associated with the use of plant extracts, fungi, bacteria or essential oils. These methods are a promising alternative to conventional approaches which can minimize the use of hazardous substances. The silver nanoparticles synthesis using red tea infusion as a reducing and stabilizing agent and their characteristics have been described. Total antioxidant capacity using DPPH radical and total content of phenolic compounds by Folin-Ciocalteau method were measured in tea infusion. Synthesis of silver nanoparticles was carried out using chemical reduction at various temperatures. Furthermore, the effect of tea infusion volume added to reaction mixture on nanoparticles’ properties was investigated. Finally, nanosilver suspensions were characterized by UV-vis spectrophotometer, dynamic light scattering (DLS) scanning electron microscope (SEM) and transmission electron microscope (TEM). Moreover, phytotoxicity of silver nanoparticles was determined using Phytotestkit microbiotest.

  7. Sulfonated macro-RAFT agents for the surfactant-free synthesis of cerium oxide-based hybrid latexes.

    PubMed

    Garnier, Jérôme; Warnant, Jérôme; Lacroix-Desmazes, Patrick; Dufils, Pierre-Emmanuel; Vinas, Jérôme; van Herk, Alex

    2013-10-01

    Three types of amphiphatic macro-RAFT agents were employed as compatibilizers to promote the polymerization reaction at the surface of nanoceria for the synthesis of CeO2-based hybrid latexes. Macro-RAFT copolymers and terpolymers were first synthesized employing various combinations of butyl acrylate as a hydrophobic monomer and acrylic acid (AA) and/or 2-acrylamido-2-methylpropane sulfonic acid (AMPS) as hydrophilic monomers. After characterizing the adsorption of these macro-RAFT agents at the cerium oxide surface by UV-visible spectrometry, emulsion copolymerization reactions of styrene and methyl acrylate were then carried out in the presence of the surface-modified nanoceria. Dynamic Light Scattering and cryo-Transmission Electron Microscopy were employed to confirm the hybrid structure of the final CeO2/polymer latexes, and proved that the presence of acrylic acid units in amphiphatic macro-RAFT agents enabled an efficient formation of hybrid structures, while the presence of AMPS units, when combined with AA units, resulted in a better distribution of cerium oxide nanoclusters between latex particles. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. 37 CFR 201.38 - Designation of agent to receive notification of claimed infringement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... person signing the Notice, and by the date of signature. (e) Filing. A service provider may file the.... The Copyright Office does not provide printed forms for filing an Interim Designation of Agent to... shall be accompanied by a filing fee for Recordation of an Interim Designation of Agent to Receive...

  9. Discovery-Synthesis, Design, and Prediction of Chalcogenide Phases

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

    Kanatzidis, Mercouri G.

    The discovery of new materials and their efficient syntheses is a fundamental goal of chemistry. A related objective is to identify foundational and rational approaches to enhance the art of synthesis by combining the exquisite predictability of organic synthesis with the high yields of solid-state chemistry. In contrast to so-called solid-state methods, inorganic syntheses in liquid fluxes permit bond formation, framework assembly, and crystallization at lower temperatures because of facile diffusion and chemical reactions with and within the flux itself. The fluxes are bona fide solvents similar to conventional organic or aqueous solvents. Such reactions can produce a wide rangemore » of materials, often metastable, from oxides to intermetallics, but typically the formation mechanisms are poorly understood. This article discusses how one can design, perform, observe, understand, and engineer the formation of compounds from inorganic melts. The focus is also design concepts such as "dimensional reduction", "phase homologies", and "panoramic synthesis", and their broad applicability. When well-defined building blocks are present and stable in the reaction, prospects for increased structural diversity and product control increase substantially. Common structural motifs within these materials systems may be related to structural precursors in the melt that may be controlled by tuning reaction conditions and composition. Stabilization of a particular building block is often accomplished with tuning of the flux composition, which controls the Lewis basicity and redox potential. In such tunable and dynamic fluxes, the synthesis can be directed toward new materials. Using complementary techniques of in situ X-ray diffraction, we can create time-dependent maps of reaction space and probe the mobile species present in melts. Lastly, certain thoughts toward the ultimate goal of targeted materials synthesis by controlling inorganic melt chemistry are discussed.« less

  10. Discovery-Synthesis, Design, and Prediction of Chalcogenide Phases

    DOE PAGES

    Kanatzidis, Mercouri G.

    2017-03-09

    The discovery of new materials and their efficient syntheses is a fundamental goal of chemistry. A related objective is to identify foundational and rational approaches to enhance the art of synthesis by combining the exquisite predictability of organic synthesis with the high yields of solid-state chemistry. In contrast to so-called solid-state methods, inorganic syntheses in liquid fluxes permit bond formation, framework assembly, and crystallization at lower temperatures because of facile diffusion and chemical reactions with and within the flux itself. The fluxes are bona fide solvents similar to conventional organic or aqueous solvents. Such reactions can produce a wide rangemore » of materials, often metastable, from oxides to intermetallics, but typically the formation mechanisms are poorly understood. This article discusses how one can design, perform, observe, understand, and engineer the formation of compounds from inorganic melts. The focus is also design concepts such as "dimensional reduction", "phase homologies", and "panoramic synthesis", and their broad applicability. When well-defined building blocks are present and stable in the reaction, prospects for increased structural diversity and product control increase substantially. Common structural motifs within these materials systems may be related to structural precursors in the melt that may be controlled by tuning reaction conditions and composition. Stabilization of a particular building block is often accomplished with tuning of the flux composition, which controls the Lewis basicity and redox potential. In such tunable and dynamic fluxes, the synthesis can be directed toward new materials. Using complementary techniques of in situ X-ray diffraction, we can create time-dependent maps of reaction space and probe the mobile species present in melts. Lastly, certain thoughts toward the ultimate goal of targeted materials synthesis by controlling inorganic melt chemistry are discussed.« less

  11. 47 CFR 7.18 - Procedure; designation of agents for service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Procedure; designation of agents for service. 7.18 Section 7.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.18 Procedure; designation...

  12. 47 CFR 7.18 - Procedure; designation of agents for service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Procedure; designation of agents for service. 7.18 Section 7.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.18 Procedure; designation...

  13. 47 CFR 7.18 - Procedure; designation of agents for service.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Procedure; designation of agents for service. 7.18 Section 7.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.18 Procedure; designation...

  14. 47 CFR 7.18 - Procedure; designation of agents for service.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Procedure; designation of agents for service. 7.18 Section 7.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.18 Procedure; designation...

  15. 47 CFR 7.18 - Procedure; designation of agents for service.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Procedure; designation of agents for service. 7.18 Section 7.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.18 Procedure; designation...

  16. 3-methyl-2-phenyl-1-substituted-indole derivatives as indomethacin analogs: design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents.

    PubMed

    Abdellatif, Khaled R A; Lamie, Phoebe F; Omar, Hany A

    2016-01-01

    In a new group of 3-methyl-2-phenyl-1-substituted-indole derivatives (10a-f), the indomethacin analogs were prepared via the Fisher indole synthesis reaction of propiophenone with appropriately substituted phenylhydrazine hydrochloride. This is followed by the insertion of the appropriate benzyl or benzoyl fragment. All the synthesized compounds were evaluated for their anti-inflammatory (in vitro and in vivo) and analgesic activities. The methanesulphonyl derivatives 10d, e and f showed the highest anti-inflammatory (in vitro and in vivo) and analgesic activities. In addition, molecular docking studies were performed on compounds 10a-f and the results were in agreement with that obtained from the in vitro COX inhibition assays. The significant anti-inflammatory and analgesic activities exhibited by 10d and 10e warrant continued preclinical development as potential anti-inflammatory and analgesic agents.

  17. Designing Agent Collectives For Systems With Markovian Dynamics

    NASA Technical Reports Server (NTRS)

    Wolpert, David H.; Lawson, John W.; Clancy, Daniel (Technical Monitor)

    2001-01-01

    The "Collective Intelligence" (COIN) framework concerns the design of collectives of agents so that as those agents strive to maximize their individual utility functions, their interaction causes a provided "world" utility function concerning the entire collective to be also maximized. Here we show how to extend that framework to scenarios having Markovian dynamics when no re-evolution of the system from counter-factual initial conditions (an often expensive calculation) is permitted. Our approach transforms the (time-extended) argument of each agent's utility function before evaluating that function. This transformation has benefits in scenarios not involving Markovian dynamics, in particular scenarios where not all of the arguments of an agent's utility function are observable. We investigate this transformation in simulations involving both linear and quadratic (nonlinear) dynamics. In addition, we find that a certain subset of these transformations, which result in utilities that have low "opacity (analogous to having high signal to noise) but are not "factored" (analogous to not being incentive compatible), reliably improve performance over that arising with factored utilities. We also present a Taylor Series method for the fully general nonlinear case.

  18. Rational design, synthesis and biological screening of triazine-triazolopyrimidine hybrids as multitarget anti-Alzheimer agents.

    PubMed

    Jameel, Ehtesham; Meena, Poonam; Maqbool, Mudasir; Kumar, Jitendra; Ahmed, Waqar; Mumtazuddin, Syed; Tiwari, Manisha; Hoda, Nasimul; Jayaram, B

    2017-08-18

    In our endeavor towards the development of potent multitarget ligands for the treatment of Alzheimer's disease, a series of triazine-triazolopyrimidine hybrids were designed, synthesized and characterized by various spectral techniques. Docking and scoring techniques were used to design the inhibitors and to display their interaction with key residues of active site. Organic synthesis relied upon convergent synthetic routes were mono and di-substituted triazines were connected with triazolopyrimidine using piperazine as a linker. In total, seventeen compounds were synthesized in which the di-substituted triazine-triazolopyrimidine derivatives 9a-d showed better acetylcholinesterase (AChE) inhibitory activity than the corresponding tri-substituted triazine-triazolopyrimidine derivatives 10a-f. Out of the disubstituted triazine-triazolopyrimidine based compounds, 9a and 9b showed encouraging inhibitory activity on AChE with IC 50 values 0.065 and 0.092 μM, respectively. Interestingly, 9a and 9b also demonstrated good inhibition selectivity towards AChE over BuChE by ∼28 folds. Furthermore, kinetic analysis and molecular modeling studies showed that 9a and 9b target both catalytic active site as well as peripheral anionic site of AChE. In addition, these derivatives effectively modulated Aβ self-aggregation as investigated through CD spectroscopy, ThT fluorescence assay and electron microscopy. Besides, these compounds exhibited potential antioxidants (2.15 and 2.91 trolox equivalent by ORAC assay) and metal chelating properties. In silico ADMET profiling highlighted that, these novel triazine derivatives have appropriate drug like properties and possess very low toxic effects in the primarily pharmacokinetic study. Overall, the multitarget profile exerted by these novel triazine molecules qualified them as potential anti-Alzheimer drug candidates in AD therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Designing a multiroute synthesis scheme in combinatorial chemistry.

    PubMed

    Akavia, Adi; Senderowitz, Hanoch; Lerner, Alon; Shamir, Ron

    2004-01-01

    Solid-phase mix-and-split combinatorial synthesis is often used to produce large arrays of compounds to be tested during the various stages of the drug development process. This method can be represented by a synthesis graph in which nodes correspond to grow operations and arcs to beads transferred among the different reaction vessels. In this work, we address the problem of designing such a graph which maximizes the number of produced target compounds (namely, compounds out of an input library of desired molecules), given constraints on the number of beads used for library synthesis and on the number of reaction vessels available for concurrent grow steps. We present a heuristic based on a discrete search for solving this problem, test our solution on several data sets, explore its behavior, and show that it achieves good performance.

  20. Gum ghatti mediated, one pot green synthesis of optimized gold nanoparticles: Investigation of process-variables impact using Box-Behnken based statistical design.

    PubMed

    Alam, Md Sabir; Garg, Arun; Pottoo, Faheem Hyder; Saifullah, Mohammad Khalid; Tareq, Abu Izneid; Manzoor, Ovais; Mohsin, Mohd; Javed, Md Noushad

    2017-11-01

    Due to unique inherent catalytic characteristics of different size, shape and surface functionalized gold nanoparticles, their potential applications, are being explored in various fields such as drug delivery, biosensor, diagnosis and theranostics. However conventional process for synthesis of these metallic nanoparticles utilizes toxic reagents as reducing agents, additional capping agent for stability as well as surface functionalization for drug delivery purposes. Hence, in this work suitability of gum Ghatti for reducing, capping and surface functionalization during the synthesis of stable Gold nanoparticles were duly explored. Role and impact of key process variables i.e. volume of chloroauric acid solution, gum solution and temperature at their respective three different levels, as well as mechanism of formation of optimized gold nanoparticles were also investigated using Box- Behnken design. These novel synthesized optimized Gold nanoparticles were further characterized by UV spectrophotometer for its surface plasmon resonance (SPR) at around ∼530nm, dynamic light scattering (DLS) for its hydrodynamic size (112.5nm), PDI (0.222) and zeta potential (-21.3mV) while, transmission electron microscopy (TEM) further revealed surface geometry of these nanoparticles being spherical in shape. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. The synthesis and dynamics research of new curing agent for epoxy resin

    NASA Astrophysics Data System (ADS)

    Peng, Yongli; Huang, Hengyu; Sun, Yong

    2017-05-01

    Two-step synthesis of trimellitic anhydride trimellitic anhydride n - butyl ester (TMNB) was introduced which could be used as an epoxy resin curing agent. The kinetics of the curing reaction was analyzed by N-order model and autocatalytic model. The curing kinetics parameters, the results show that the curing activation energy (Ea) of this system was 35.79kJ / mol. The kinetic equation of curing was d/a d t =2.1061 ×104e x p (-35.79/R T ) α0.5163(l-α ) 0.366 . Combined with β-1 / T extrapolation and experimental adjustment to obtain the resin system curing process: 75°C for 1h, 140°C for 3h, 160°C for 2h.

  2. QSAR-driven design, synthesis and discovery of potent chalcone derivatives with antitubercular activity.

    PubMed

    Gomes, Marcelo N; Braga, Rodolpho C; Grzelak, Edyta M; Neves, Bruno J; Muratov, Eugene; Ma, Rui; Klein, Larry L; Cho, Sanghyun; Oliveira, Guilherme R; Franzblau, Scott G; Andrade, Carolina Horta

    2017-09-08

    New anti-tuberculosis (anti-TB) drugs are urgently needed to battle drug-resistant Mycobacterium tuberculosis strains and to shorten the current 6-12-month treatment regimen. In this work, we have continued the efforts to develop chalcone-based anti-TB compounds by using an in silico design and QSAR-driven approach. Initially, we developed SAR rules and binary QSAR models using literature data for targeted design of new heteroaryl chalcone compounds with anti-TB activity. Using these models, we prioritized 33 compounds for synthesis and biological evaluation. As a result, 10 heteroaryl chalcone compounds (4, 8, 9, 11, 13, 17-20, and 23) were found to exhibit nanomolar activity against replicating mycobacteria, low micromolar activity against nonreplicating bacteria, and nanomolar and micromolar against rifampin (RMP) and isoniazid (INH) monoresistant strains (rRMP and rINH) (<1 μM and <10 μM, respectively). The series also show low activity against commensal bacteria and generally show good selectivity toward M. tuberculosis, with very low cytotoxicity against Vero cells (SI = 11-545). Our results suggest that our designed heteroaryl chalcone compounds, due to their high potency and selectivity, are promising anti-TB agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Synthesis of Intrinsically Disordered Fluorinated Peptides for Modular Design of High-Signal 19 F MRI Agents.

    PubMed

    Kirberger, Steven E; Maltseva, Sofia D; Manulik, Joseph C; Einstein, Samuel A; Weegman, Bradley P; Garwood, Michael; Pomerantz, William C K

    2017-06-01

    19 F MRI is valuable for in vivo imaging due to the only trace amounts of fluorine in biological systems. Because of the low sensitivity of MRI however, designing new fluorochemicals remains a significant challenge for achieving sufficient 19 F signal. Here, we describe a new class of high-signal, water-soluble fluorochemicals as 19 F MRI imaging agents. A polyamide backbone is used for tuning the proteolytic stability to avoid retention within the body, which is a limitation of current state-of-the-art perfluorochemicals. We show that unstructured peptides containing alternating N-ϵ-trifluoroacetyllysine and lysine provide a degenerate 19 F NMR signal. 19 F MRI phantom images provide sufficient contrast at micromolar concentrations, showing promise for eventual clinical applications. Finally, the degenerate high signal characteristics were retained when conjugated to a large protein, indicating potential for in vivo targeting applications, including molecular imaging and cell tracking. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguy&Ecirtil; N. Thi&Cmb. B. Dot; Kim

    2016-02-01

    Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high saturation magnetization value (84.5 emu g-1). The surface of the IONPs could be tailored post synthesis with two different ligands which provided functionality and stability in water and phosphate buffer saline (PBS). Their potential as a magnetic resonance imaging (MRI) contrast agent was confirmed as they exhibited high r1 and r2 relaxivities of 7.95 mM-1 s-1 and 185.58 mM-1 s-1 respectively at 1.4 T. Biocompatibility and viability of IONPs in primary human mesenchymal stem cells (hMSCs) was studied and confirmed.Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high

  5. Designing of Roaming Protocol for Bluetooth Equipped Multi Agent Systems

    NASA Astrophysics Data System (ADS)

    Subhan, Fazli; Hasbullah, Halabi B.

    Bluetooth is an established standard for low cost, low power, wireless personal area network. Currently, Bluetooth does not support any roaming protocol in which handoff occurs dynamically when a Bluetooth device is moving out of the piconet. If a device is losing its connection to the master device, no provision is made to transfer it to another master. Handoff is not possible in a piconet, as in order to stay within the network, a slave would have to keep the same master. So, by definition intra-handoff is not possible within a piconet. This research mainly focuses on Bluetooth technology and designing a roaming protocol for Bluetooth equipped multi agent systems. A mathematical model is derived for an agent. The idea behind the mathematical model is to know when to initiate the roaming process for an agent. A desired trajectory for the agent is calculated using its x and y coordinates system, and is simulated in SIMULINK. Various roaming techniques are also studied and discussed. The advantage of designing a roaming protocol is to ensure the Bluetooth enabled roaming devices can freely move inside the network coverage without losing its connection or break of service in case of changing the base stations.

  6. 76 FR 30437 - Indian Child Welfare Act; Designated Tribal Agents for Service of Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-25

    ...The regulations implementing the Indian Child Welfare Act provide that Indian tribes may designate an agent other than the tribal chairman for service of notice of proceedings under the Act. This notice includes the current list of designated tribal agents for service of notice.

  7. 25 CFR 23.12 - Designated tribal agent for service of notice.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... pursuant to 25 U.S.C. 1912 may designate by resolution, or by such other form as the tribe's constitution... shall update and publish as necessary the names and addresses of the designated agents in the Federal...

  8. Design and synthesis of type-III mimetics of ShK toxin

    NASA Astrophysics Data System (ADS)

    Baell, Jonathan B.; Harvey, Andrew J.; Norton, Raymond S.

    2002-04-01

    ShK toxin is a structurally defined, 35-residue polypeptide which blocks the voltage-gated Kv1.3 potassium channel in T-lymphocytes and has been identified as a possible immunosuppressant. Our interest lies in the rational design and synthesis of type-III mimetics of protein and polypeptide structure and function. ShK toxin is a challenging target for mimetic design as its binding epitope consists of relatively weakly binding residues, some of which are discontinuous. We discuss here our investigations into the design and synthesis of 1st generation, small molecule mimetics of ShK toxin and highlight any principles relevant to the generic design of type-III mimetics of continuous and discontinuous binding epitopes. We complement our approach with attempted pharmacophore-based database mining.

  9. Synthesis of tritium-labeled cyadox, a promising antimicrobial growth-promoting agent with high specific activity.

    PubMed

    Harnud, Sechenchogt; Zhang, Aiqun; Yuan, Zonghui

    2018-05-23

    Cyadox is a new antimicrobial growth-promoting agent for food-producing animals. Studies on radiolabeled compounds enable the use of sensitive radiometric analytical methods and help in the elucidation of metabolic and elimination pathways. In the present study, 6-[ 3 H]-cyadox with a high specific activity of 2.08 Ci/mmol was prepared by the catalytic bromine-tritium exchange of 4-bromo-2-nitroaniline followed by a three-step microscale synthesis, giving a high yield between 36.16% and 94.75%. Copyright © 2018. Published by Elsevier Ltd.

  10. Design, synthesis, and biological evaluation of a novel series of quercetin diacylglucosides as potent anti-MRSA and anti-VRE agents.

    PubMed

    Hossion, Abugafar M L; Otsuka, Nao; Kandahary, Rafiya K; Tsuchiya, Tomofusa; Ogawa, Wakano; Iwado, Akimasa; Zamami, Yoshito; Sasaki, Kenji

    2010-09-01

    A series of novel quercetin diacylglucosides were designed and first synthesized by Steglich esterification on the basis of MRSA strains inhibiting natural compound A. The in vitro inhibition of different multi-drug resistant bacterial strains and Escherichia coli DNA gyrase B was investigated. In the series, compound 10h was up to 128-fold more potent against vancomycin-resistant enterococci and more effective than A, which represents a promising new candidate as a potent anti-MRSA and anti-VRE agent. Copyright 2010. Published by Elsevier Ltd.

  11. Nonlinear multivariable design by total synthesis. [of gas turbine engine control systems

    NASA Technical Reports Server (NTRS)

    Sain, M. K.; Peczkowski, J. L.

    1982-01-01

    The Nominal Design Problem (NDP) is extended to nonlinear cases, and a new case study of robust feedback synthesis for gas turbine control design is presented. The discussion of NDP extends and builds on earlier Total Synthesis Problem theory and ideas. Some mathematical preliminaries are given in which a bijection from a set S onto a set T is considered, with T admitting the structure of an F-vector space. NDP is then discussed for a nonlinear plant, and nonlinear nominal design is defined and characterized. The design of local controllers for a turbojet and the scheduling of these controls into a global control are addressed.

  12. Synthesis and evaluation of 1-amino-6-halo-β-carbolines as antimalarial and antiprion agents.

    PubMed

    Thompson, Mark J; Louth, Jennifer C; Little, Susan M; Jackson, Matthew P; Boursereau, Yohan; Chen, Beining; Coldham, Iain

    2012-04-01

    Malaria is one of the world's most devastating parasitic diseases, causing almost one million deaths each year. Growing resistance to classical antimalarial drugs, such as chloroquine, necessitates the discovery of new therapeutic agents for successful control of this global disease. Here, we report the synthesis of some 6-halo-β-carbolines as analogues of the potent antimalarial natural product, manzamine A, retaining its heteroaromatic core whilst providing compounds with much improved synthetic accessibility. Two compounds displayed superior activity to chloroquine itself against a resistant Plasmodium falciparum strain, identifying them as promising leads for future development. Furthermore, in line with previous reports of similarities in antimalarial and antiprion effects of aminoaryl-based antimalarial agents, the 1-amino-β-carboline libraries were also found to possess significant bioactivity against a prion-infected cell line. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. System Synthesis in Preliminary Aircraft Design using Statistical Methods

    NASA Technical Reports Server (NTRS)

    DeLaurentis, Daniel; Mavris, Dimitri N.; Schrage, Daniel P.

    1996-01-01

    This paper documents an approach to conceptual and preliminary aircraft design in which system synthesis is achieved using statistical methods, specifically design of experiments (DOE) and response surface methodology (RSM). These methods are employed in order to more efficiently search the design space for optimum configurations. In particular, a methodology incorporating three uses of these techniques is presented. First, response surface equations are formed which represent aerodynamic analyses, in the form of regression polynomials, which are more sophisticated than generally available in early design stages. Next, a regression equation for an overall evaluation criterion is constructed for the purpose of constrained optimization at the system level. This optimization, though achieved in a innovative way, is still traditional in that it is a point design solution. The methodology put forward here remedies this by introducing uncertainty into the problem, resulting a solutions which are probabilistic in nature. DOE/RSM is used for the third time in this setting. The process is demonstrated through a detailed aero-propulsion optimization of a high speed civil transport. Fundamental goals of the methodology, then, are to introduce higher fidelity disciplinary analyses to the conceptual aircraft synthesis and provide a roadmap for transitioning from point solutions to probabalistic designs (and eventually robust ones).

  14. In vivo antimicrobial activity of silver nanoparticles produced via a green chemistry synthesis using Acacia rigidula as a reducing and capping agent.

    PubMed

    Escárcega-González, Carlos Enrique; Garza-Cervantes, J A; Vázquez-Rodríguez, A; Montelongo-Peralta, Liliana Zulem; Treviño-González, M T; Díaz Barriga Castro, E; Saucedo-Salazar, E M; Chávez Morales, R M; Regalado Soto, D I; Treviño González, F M; Carrazco Rosales, J L; Cruz, Rocío Villalobos; Morones-Ramírez, José Rubén

    2018-01-01

    One of the main issues in the medical field and clinical practice is the development of novel and effective treatments against infections caused by antibiotic-resistant bacteria. One avenue that has been approached to develop effective antimicrobials is the use of silver nanoparticles (Ag-NPs), since they have been found to exhibit an efficient and wide spectrum of antimicrobial properties. Among the main drawbacks of using Ag-NPs are their potential cytotoxicity against eukaryotic cells and the latent environmental toxicity of their synthesis methods. Therefore, diverse green synthesis methods, which involve the use of environmentally friendly plant extracts as reductive and capping agents, have become attractive to synthesize Ag-NPs that exhibit antimicrobial effects against resistant bacteria at concentrations below toxicity thresholds for eukaryotic cells. In this study, we report a green one-pot synthesis method that uses Acacia rigidula extract as a reducing and capping agent, to produce Ag-NPs with applications as therapeutic agents to treat infections in vivo. The Ag-NPs were characterized using transmission electron microscopy (TEM), high-resolution TEM, selected area electron diffraction, energy-dispersive spectroscopy, ultraviolet-visible, and Fourier transform infrared. We show that Ag-NPs are spherical with a narrow size distribution. The Ag-NPs show antimicrobial activities in vitro against Gram-negative ( Escherichia coli , Pseudomonas aeruginosa , and a clinical multidrug-resistant strain of P. aeruginosa ) and Gram-positive ( Bacillus subtilis ) bacteria. Moreover, antimicrobial effects of the Ag-NPs, against a resistant P. aeruginosa clinical strain, were tested in a murine skin infection model. The results demonstrate that the Ag-NPs reported in this work are capable of eradicating pathogenic resistant bacteria in an infection in vivo. In addition, skin, liver, and kidney damage profiles were monitored in the murine infection model, and the

  15. In vivo antimicrobial activity of silver nanoparticles produced via a green chemistry synthesis using Acacia rigidula as a reducing and capping agent

    PubMed Central

    Escárcega-González, Carlos Enrique; Garza-Cervantes, JA; Vázquez-Rodríguez, A; Montelongo-Peralta, Liliana Zulem; Treviño-González, MT; Díaz Barriga Castro, E; Saucedo-Salazar, EM; Chávez Morales, RM; Regalado Soto, DI; Treviño González, FM; Carrazco Rosales, JL; Cruz, Rocío Villalobos; Morones-Ramírez, José Rubén

    2018-01-01

    Introduction One of the main issues in the medical field and clinical practice is the development of novel and effective treatments against infections caused by antibiotic-resistant bacteria. One avenue that has been approached to develop effective antimicrobials is the use of silver nanoparticles (Ag-NPs), since they have been found to exhibit an efficient and wide spectrum of antimicrobial properties. Among the main drawbacks of using Ag-NPs are their potential cytotoxicity against eukaryotic cells and the latent environmental toxicity of their synthesis methods. Therefore, diverse green synthesis methods, which involve the use of environmentally friendly plant extracts as reductive and capping agents, have become attractive to synthesize Ag-NPs that exhibit antimicrobial effects against resistant bacteria at concentrations below toxicity thresholds for eukaryotic cells. Purpose In this study, we report a green one-pot synthesis method that uses Acacia rigidula extract as a reducing and capping agent, to produce Ag-NPs with applications as therapeutic agents to treat infections in vivo. Materials and methods The Ag-NPs were characterized using transmission electron microscopy (TEM), high-resolution TEM, selected area electron diffraction, energy-dispersive spectroscopy, ultraviolet–visible, and Fourier transform infrared. Results We show that Ag-NPs are spherical with a narrow size distribution. The Ag-NPs show antimicrobial activities in vitro against Gram-negative (Escherichia coli, Pseudomonas aeruginosa, and a clinical multidrug-resistant strain of P. aeruginosa) and Gram-positive (Bacillus subtilis) bacteria. Moreover, antimicrobial effects of the Ag-NPs, against a resistant P. aeruginosa clinical strain, were tested in a murine skin infection model. The results demonstrate that the Ag-NPs reported in this work are capable of eradicating pathogenic resistant bacteria in an infection in vivo. In addition, skin, liver, and kidney damage profiles were

  16. Designed Single-Step Synthesis, Structure, and Derivative Textural Properties of Well-Ordered Layered Penta-Coordinate Silicon Alcoholate Complexes

    PubMed Central

    Li, Xiansen; Michaelis, Vladimir K.; Ong, Ta-Chung; Smith, Stacey J.; Griffin, Robert G.; Wang, Evelyn N.

    2014-01-01

    The controllable synthesis of well-ordered layered materials with specific nanoarchitecture poses a grand challenge in materials chemistry. We report the solvothermal synthesis of two structurally analogous 5-coordinate organosilicate complexes via a novel transesterification mechanism. Since the polycrystalline nature of the intrinsic hypervalent Si complex thwarts the endeavor in determining its structure, a novel strategy concerning the elegant addition of a small fraction of B species as an effective crystal growth mediator and a sacrificial agent is proposed to directly prepare diffraction-quality single crystals without disrupting the intrinsic elemental type. In the determined crystal structure, two monomeric primary building units (PBUs) self-assemble into a dimeric asymmetric secondary BU via strong Na+-O2− ionic bonds. The designed one-pot synthesis is straightforward, robust, and efficient, leading to a well-ordered (10ī)-parallel layered Si complex with its principal interlayers intercalated with extensive van der Waals gaps in spite of the presence of substantial Na+ counterions as a result of unique atomic arrangement in its structure. On the other hand, upon fast pyrolysis, followed by acid leaching, both complexes are converted into two SiO2 composites bearing BET surface areas of 163.3 and 254.7 m2 g−1 for the pyrolyzed intrinsic and B-assisted Si complexes, respectively. The transesterification methodology merely involving alcoholysis but without any hydrolysis side reaction is designed to have generalized applicability for use in synthesizing new layered metal-organic compounds with tailored PBUs and corresponding metal oxide particles with hierarchical porosity. PMID:24737615

  17. Expediting analog design retargeting by design knowledge re-use and circuit synthesis: a practical example on a Delta-Sigma modulator

    NASA Astrophysics Data System (ADS)

    Webb, Matthew; Tang, Hua

    2016-08-01

    In the past decade or two, due to constant and rapid technology changes, analog design re-use or design retargeting to newer technologies has been brought to the table in order to expedite the design process and improve time-to-market. If properly conducted, analog design retargeting could significantly cut down design cycle compared to designs starting from the scratch. In this article, we present an empirical and general method for efficient analog design retargeting by design knowledge re-use and circuit synthesis (CS). The method first identifies circuit blocks that compose the source system and extracts the performance parameter specifications of each circuit block. Then, for each circuit block, it scales the values of design variables (DV) from the source design to derive an initial design in the target technology. Depending on the performance of this initial target design, a design space is defined for synthesis. Subsequently, each circuit block is automatically synthesised using state-of-art analog synthesis tools based on a combination of global and local optimisation techniques to achieve comparable performance specifications to those extracted from the source system. Finally, the overall system is composed of those synthesised circuit blocks in the target technology. We illustrate the method using a practical example of a complex Delta-Sigma modulator (DSM) circuit.

  18. Application of advanced multidisciplinary analysis and optimization methods to vehicle design synthesis

    NASA Technical Reports Server (NTRS)

    Consoli, Robert David; Sobieszczanski-Sobieski, Jaroslaw

    1990-01-01

    Advanced multidisciplinary analysis and optimization methods, namely system sensitivity analysis and non-hierarchical system decomposition, are applied to reduce the cost and improve the visibility of an automated vehicle design synthesis process. This process is inherently complex due to the large number of functional disciplines and associated interdisciplinary couplings. Recent developments in system sensitivity analysis as applied to complex non-hierarchic multidisciplinary design optimization problems enable the decomposition of these complex interactions into sub-processes that can be evaluated in parallel. The application of these techniques results in significant cost, accuracy, and visibility benefits for the entire design synthesis process.

  19. New Potential Antimalarial Agents: Design, Synthesis and Biological Evaluation of Some Novel Quinoline Derivatives as Antimalarial Agents.

    PubMed

    Radini, Ibrahim Ali M; Elsheikh, Tarek M Y; El-Telbani, Emad M; Khidre, Rizk E

    2016-07-14

    A novel series of dihydropyrimidines (DHPMs) 4a-j; 2-oxopyran-3-carboxylate 7a,b; 1-amino-1,2-dihydropyridine-3-carboxylate 8; and 1,3,4-oxadiazole derivatives 12 with quinolinyl residues have been synthesized in fairly good yields. The structure of the newly synthesized compounds was elucidated on the basis of analytical and spectral analyses. In vitro antimalarial evaluation of the synthesized quinoline derivatives against Plasmodium falciparum revealed them to possess moderate to high antimalarial activities, with IC50 values ranging from 0.014-5.87 μg/mL. Compounds 4b,g,i and 12 showed excellent antimalarial activity against to Plasmodium falciparum compared with the antimalarial agent chloroquine (CQ).

  20. DNA synthesis inhibitors for the treatment of gastrointestinal cancer.

    PubMed

    Yasui, Hiroshi; Tsurita, Giichiro; Imai, Kohzoh

    2014-11-01

    Intensive laboratory, preclinical and clinical studies have identified and validated molecular targets in cancers, leading to a shift toward the development of novel, rationally designed and specific therapeutic agents. However, gastrointestinal cancers continue to have a poor prognosis, largely due to drug resistance. Here, we discuss the current understanding of DNA synthesis inhibitors and their mechanisms of action for the treatment of gastrointestinal malignancies. Conventional agents, including DNA synthesis inhibitors such as fluoropyrimidines and platinum analogs, remain the most effective therapeutics and are the standards against which new drugs are compared. Novel DNA synthesis inhibitors for the treatment of gastrointestinal malignancies include a combination of the antimetabolite TAS-102, which consists of trifluorothymidine with a thymidine phosphorylase inhibitor, and a novel micellar formulation of cisplatin NC-6004 that uses a nanotechnology-based drug delivery system. The challenges of translational cancer research using DNA synthesis inhibitors include the identification of drugs that are specific to tumor cells to reduce toxicity and increase antitumor efficacy, biomarkers to predict pharmacological responses to chemotherapeutic drugs, identification of ways to overcome drug resistance and development of novel combination therapies with DNA synthesis inhibitors and other cancer therapies, such as targeted molecular therapeutics. Here, we discuss the current understanding of DNA synthesis inhibitors and their mechanisms of action for the treatment of gastrointestinal malignancies.

  1. Design of Protease Activated Optical Contrast Agents That Exploit a Latent Lysosomotropic Effect for Use in Fluorescence-Guided Surgery

    PubMed Central

    2015-01-01

    There is a need for new molecular-guided contrast agents to enhance surgical procedures such as tumor resection that require a high degree of precision. Cysteine cathepsins are highly up-regulated in a wide variety of cancers, both in tumor cells and in the tumor-supporting cells of the surrounding stroma. Therefore, tools that can be used to dynamically monitor their activity in vivo could be used as imaging contrast agents for intraoperative fluorescence image guided surgery (FGS). Although multiple classes of cathepsin-targeted substrate probes have been reported, most suffer from overall fast clearance from sites of protease activation, leading to reduced signal intensity and duration in vivo. Here we describe the design and synthesis of a series of near-infrared fluorogenic probes that exploit a latent cationic lysosomotropic effect (LLE) to promote cellular retention upon protease activation. These probes show tumor-specific retention, fast activation kinetics, and rapid systemic distribution. We demonstrate that they are suitable for detection of diverse cancer types including breast, colon and lung tumors. Most importantly, the agents are compatible with the existing, FDA approved, da Vinci surgical system for fluorescence guided tumor resection. Therefore, our data suggest that the probes reported here can be used with existing clinical instrumentation to detect tumors and potentially other types of inflammatory lesions to guide surgical decision making in real time. PMID:26039341

  2. Novel sarsasapogenin-triazolyl hybrids as potential anti-Alzheimer's agents: Design, synthesis and biological evaluation.

    PubMed

    Wang, Wenbao; Wang, Wei; Yao, Guodong; Ren, Qiang; Wang, Di; Wang, Zedan; Liu, Peng; Gao, Pinyi; Zhang, Yan; Wang, Shaojie; Song, Shaojiang

    2018-05-10

    Sarsasapogenin, an active ingredient in Rhizoma anemarrhenae, is a promising bioactive lead compound in the treatment of Alzheimer's disease. To search for more efficient anti-Alzheimer agents, a series of novel sarsasapogenin-triazolyl hybrids were designed, synthesized, and evaluated for their Aβ 1-42 aggregation inhibitory activities. Most of these new hybrids displayed potent Aβ 1-42 aggregation inhibition. In particular, the promising compounds 6j and 6o displayed a better ability to interrupt the formation of Aβ 1-42 fibrils than curcumin. Moreover, 6j and 6o exhibited moderate neuroprotective effects against H 2 O 2 -induced neurotoxicity in SH-SY5Y cells. To investigate whether 6j and 6o could improve cognitive deficits, we performed behavioral tests to examine the learning and memory impairments induced by intracerebroventricular injection of Aβ 1-42 (ICV-Aβ 1-42 ) in mice and TUNEL staining to observe neuronal apoptosis in the hippocampus. The results obtained indicated that oral treatment with 6j and 6o significantly ameliorated cognitive impairments in behavioral tests and TUNEL staining showed that 6j and 6o attenuated neuronal loss in the brain. Taken together, the results we obtained showed that the sarsasapogenin skeleton could be a promising structural template for the development of new anti-Alzheimer drug candidates, and compounds 6j and 6o have the potential to be important lead compounds for further research. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  3. Design and synthesis of novel carbazole tethered pyrrole derivatives as potent inhibitors of Mycobacterium tuberculosis.

    PubMed

    Surineni, Goverdhan; Yogeeswari, Perumal; Sriram, Dharmarajan; Kantevari, Srinivas

    2015-02-01

    A series of novel carbazole tethered pyrrole derivatives were designed by coupling core fragments of antitubercular agents, carbazole and substituted pyrrole in single molecular architecture. The synthesis of new analogues was achieved by FeCl3 mediated one pot three component condensation of 2-nitrovinylcarbazoles with aryl or alkyl amines and dimethylacetylene dicarboxylate (DMAD). All the new analogues 5a-l and 6a-l were fully characterized by their NMR and mass spectral data. Among the twenty four new compounds screened for in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv, dimethyl 1-(4-fluorophenyl)-4-(9-methyl-9H-carbazol-3-yl)-1H-pyrrole-2,3-dicarboxylate (5b) was found to be most active with MIC 3.13μg/mL and has shown low cytotoxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. A Bayesian Dose-finding Design for Oncology Clinical Trials of Combinational Biological Agents

    PubMed Central

    Cai, Chunyan; Yuan, Ying; Ji, Yuan

    2013-01-01

    Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which efficacy and toxicity monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as an example, we propose a dose-finding design to identify the biologically optimal dose combination (BODC), which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change-point model is used to reflect the fact that the dose-toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose-efficacy relationship. During the trial, we continuously update the posterior estimates of toxicity and efficacy and assign patients to the most appropriate dose combination. We propose a novel dose-finding algorithm to encourage sufficient exploration of untried dose combinations in the two-dimensional space. Extensive simulation studies show that the proposed design has desirable operating characteristics in identifying the BODC under various patterns of dose-toxicity and dose-efficacy relationships. PMID:24511160

  5. Design, synthesis, and evaluation of resveratrol derivatives as Aß(₁-₄₂) aggregation inhibitors, antioxidants, and neuroprotective agents.

    PubMed

    Lu, Chuanjun; Guo, Yueyan; Li, Jianheng; Yao, Meicun; Liao, Qiongfeng; Xie, Zhiyong; Li, Xingshu

    2012-12-15

    A series of novel resveratrol derivatives were designed, synthesised and evaluated as potential therapeutic agents for the treatment of Alzheimer's disease. Among these compounds, compound 7l, (E)-5-(4-(isopropylamino)styryl)benzene-1,3-diol, exhibited potent ß-amyloid aggregation inhibition activity, which was confirmed by a ThT fluorescence assay (71.65% at 20 μM) and transmission electron microscopy (TEM). Compound 7l also exhibited good antioxidant activity (4.12 Trolox equivalents in an oxygen radical absorbance capacity assay and a 37% reduction in reactive oxygen species in cells at 10 μM). The cytotoxicity analysis of compounds 7f, 7i, 7j and 7l indicated that these compounds have lower toxicities than resveratrol at 60 μM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. The Design of Future Airbreathing Engine Systems within an Intelligent Synthesis Environment

    NASA Technical Reports Server (NTRS)

    Malone, J. B.; Housner, J. M.; Lytle, J. K.

    1999-01-01

    This paper describes a new Initiative proposed by the National Aeronautics and Space Administration (NASA). The purpose of this initiative is to develop a future design environment for engineering and science mission synthesis for use by NASA scientists and engineers. This new initiative is called the Intelligent Synthesis Environment (ISE). The paper describes the mission of NASA, future aerospace system characteristics, the current engineering design process, the ISE concept, and concludes with a description of possible ISE applications for the decision of air-breathing propulsion systems.

  7. Synthesis of Zinc Oxide Nanoparticles using Anthocyanin as a Capping Agent

    NASA Astrophysics Data System (ADS)

    Septiani, N. L. W.; Yuliarto, B.; Iqbal, M.; Nugraha

    2017-05-01

    Zinc Oxide nanoparticles have been successfully synthesized by utilizing anthocyanin as a capping agent by thermal decomposition of precursor route. The influence of the high and low concentrations of the anthocyanin to the shape and size of ZnO was investigated in this work. The anthocyanin was obtained from Indonesia black rice extract with methanol as a solvent. The crystallinity and morphology properties were characterized by X-Ray Diffractometer (XRD), and Scanning Electron Microscope (SEM), respectively. XRD result showed that ZnO was formed with good crystallinity without any second phase and had a hexagonal wurtzite crystal structure. SEM result revealed that ZnO with a low concentration of anthocyanin has a spherical shape with a uniform size of about 16 nm while ZnO with a high concentration of anthocyanin has a rod-like shape. The size of spherical ZnO in this work is smaller than ZnO from the same method of synthesis without anthocyanin (~30 nm).

  8. 75 FR 28103 - Indian Child Welfare Act; Designated Tribal Agents for Service of Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-19

    ...The regulations implementing the Indian Child Welfare Act provide that Indian Tribes may designate an agent other than the Tribal chairman for service of notice of proceedings under the Act. This notice includes the current list of designated Tribal agents for service of notice. The names are those received by the Secretary of the Interior before the date of this publication.

  9. Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents.

    PubMed

    Fang, Xue-Jie; Jeyakkumar, Ponmani; Avula, Srinivasa Rao; Zhou, Qian; Zhou, Cheng-He

    2016-06-01

    A series of 5-fluorouracil benzimidazoles as novel type of potential antimicrobial agents were designed and synthesized for the first time. Bioactive assay manifested that some of the prepared compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains in comparison with reference drugs norfloxacin, chloromycin and fluconazole. Noticeably, 3-fluorobenzyl benzimidazole derivative 5c gave remarkable antimicrobial activities against Saccharomyces cerevisiae, MRSA and Bacillus proteus with MIC values of 1, 2 and 4μg/mL, respectively. Experimental research revealed that compound 5c could effectively intercalate into calf thymus DNA to form compound 5c-DNA complex which might block DNA replication and thus exert antimicrobial activities. Molecular docking indicated that compound 5c should bind with DNA topoisomerase IA through three hydrogen bonds by the use of fluorine atom and oxygen atoms in 5-fluorouracil with the residue Lys 423. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

    PubMed

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

    2016-05-05

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

  11. Flow Chemistry for Designing Sustainable Chemical Synthesis (journal article)

    EPA Science Inventory

    An efficiently designed continuous flow chemical process can lead to significant advantages in developing a sustainable chemical synthesis or process. These advantages are the direct result of being able to impart a higher degree of control on several key reactor and reaction par...

  12. Synthesis and cytotoxic evaluation of novel symmetrical taspine derivatives as anticancer agents.

    PubMed

    Zhang, Jie; Zhang, Yanmin; Pan, Xiaoyan; Wang, Sicen; He, Langchon

    2011-07-01

    It has been demonstrated that taspine derivatives act as anticancer agents, thus we designed and synthesized a novel class of symmetrical biphenyl derivatives. We evaluated the cytotoxicity and antitumor activity of biphenyls against five human tumor and normal cell lines. The results indicated that the majority of the compounds exhibited anticancer activity equivalent to or greater than the positive control. Compounds (11) and (12) demonstrated the most potent cytotoxic activity with IC₅₀ values between 19.41 µM and 29.27 µM. The potent antiproliferative capabilities of these compounds against ECV304 human transformed endothelial cells indicated that these biphenyls could potentially serve as antiangiogenic agents. We also reviewed the relationship between structure and activity based on the experimental results. Our findings provide a good starting point for further development of symmetrical biphenyl derivatives as potential novel anticancer agents.

  13. Green synthesis of silver nanoparticles via plant extracts: beginning a new era in cancer theranostics.

    PubMed

    Ovais, Muhammad; Khalil, Ali Talha; Raza, Abida; Khan, Muhammad Adeeb; Ahmad, Irshad; Islam, Nazar Ul; Saravanan, Muthupandian; Ubaid, Muhammad Furqan; Ali, Muhammad; Shinwari, Zabta Khan

    2016-12-01

    With the development of the latest technologies, scientists are looking to design novel strategies for the treatment and diagnosis of cancer. Advances in medicinal plant research and nanotechnology have attracted many researchers to the green synthesis of metallic nanoparticles due to its several advantages over conventional synthesis (simple, fast, energy efficient, one pot processes, safer, economical and biocompatibility). Medicinally active plants have proven to be the best reservoirs of diverse phytochemicals for the synthesis of biogenic silver nanoparticles (AgNPs). In this review, we discuss mechanistic advances in the synthesis and optimization of AgNPs from plant extracts. Moreover, we have thoroughly discussed the recent developments and milestones achieved in the use of biogenic AgNPs as cancer theranostic agents and their proposed mechanism of action. Anticipating all of the challenges, we hope that biogenic AgNPs may become a potential cancer theranostic agent in the near future.

  14. Combinatorial synthesis and in vitro evaluation of a biaryl hydroxyketone library as antivirulence agents against MRSA.

    PubMed

    Yu, Guanping; Kuo, David; Shoham, Menachem; Viswanathan, Rajesh

    2014-02-10

    Antibiotic resistance coupled with decreased development of new antibiotics necessitates the search for novel antibacterial agents. Antivirulence agents offer an alternative to conventional antibiotics. In this work, we report on a family of small-molecule antivirulence agents against methicillin-resistant Staphylococcus aureus (MRSA), the most widespread bacterial pathogen. Structure-activity relationship studies led to the development of a concise synthesis of a 148-member biarylhydroxyketone library. An acylation bond-forming process afforded resorcinols (1) and aryloxy acetonitriles (2) as synthons. A Lewis-acid-activated Friedel-Crafts' acylation step involving a nitrile functionality of 2 by ZnCl2, followed by nucleophilic attack by 1 was executed to obtain biaryl hydroxyketones in excellent yields. A large number of products crystallized. This strategy affords a range of biarylhydroxyketones in a single step. This is the first collective synthetic study documenting access to this class of compounds through a single synthetic operation. In vitro efficacy of compounds in this library was evaluated by a rabbit erythrocyte hemolysis assay. The most efficacious compound, 4f-12, inhibits hemolysis by 98.1 ± 0.1% compared to control in the absence of the compound.

  15. A prototype computerized synthesis methodology for generic space access vehicle (SAV) conceptual design

    NASA Astrophysics Data System (ADS)

    Huang, Xiao

    2006-04-01

    Today's and especially tomorrow's competitive launch vehicle design environment requires the development of a dedicated generic Space Access Vehicle (SAV) design methodology. A total of 115 industrial, research, and academic aircraft, helicopter, missile, and launch vehicle design synthesis methodologies have been evaluated. As the survey indicates, each synthesis methodology tends to focus on a specific flight vehicle configuration, thus precluding the key capability to systematically compare flight vehicle design alternatives. The aim of the research investigation is to provide decision-making bodies and the practicing engineer a design process and tool box for robust modeling and simulation of flight vehicles where the ultimate performance characteristics may hinge on numerical subtleties. This will enable the designer of a SAV for the first time to consistently compare different classes of SAV configurations on an impartial basis. This dissertation presents the development steps required towards a generic (configuration independent) hands-on flight vehicle conceptual design synthesis methodology. This process is developed such that it can be applied to any flight vehicle class if desired. In the present context, the methodology has been put into operation for the conceptual design of a tourist Space Access Vehicle. The case study illustrates elements of the design methodology & algorithm for the class of Horizontal Takeoff and Horizontal Landing (HTHL) SAVs. The HTHL SAV design application clearly outlines how the conceptual design process can be centrally organized, executed and documented with focus on design transparency, physical understanding and the capability to reproduce results. This approach offers the project lead and creative design team a management process and tool which iteratively refines the individual design logic chosen, leading to mature design methods and algorithms. As illustrated, the HTHL SAV hands-on design methodology offers growth

  16. Structured output-feedback controller synthesis with design specifications

    NASA Astrophysics Data System (ADS)

    Hao, Yuqing; Duan, Zhisheng

    2017-03-01

    This paper considers the problem of structured output-feedback controller synthesis with finite frequency specifications. Based on the orthogonal space information of input matrix, an improved parameter-dependent Lyapunov function method is first proposed. Then, a two-stage construction method is designed, which depends on an initial centralised controller. Corresponding design conditions for three types of output-feedback controllers are presented in terms of unified representations. Moreover, heuristic algorithms are provided to explore the desirable controllers. Finally, the effectiveness of these proposed methods is illustrated via some practical examples.

  17. 47 CFR 68.418 - Procedure; designation of agents for service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Procedure; designation of agents for service. 68.418 Section 68.418 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) CONNECTION OF TERMINAL EQUIPMENT TO THE TELEPHONE NETWORK Complaint Procedures § 68...

  18. 47 CFR 14.35 - Procedure; designation of agents for service.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Procedure; designation of agents for service. 14.35 Section 14.35 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO ADVANCED COMMUNICATIONS SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Recordkeeping, Consumer Dispute Assistance, and...

  19. 47 CFR 14.35 - Procedure; designation of agents for service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Procedure; designation of agents for service. 14.35 Section 14.35 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO ADVANCED COMMUNICATIONS SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Recordkeeping, Consumer Dispute Assistance, and...

  20. 47 CFR 14.35 - Procedure; designation of agents for service.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Procedure; designation of agents for service. 14.35 Section 14.35 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO ADVANCED COMMUNICATIONS SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Recordkeeping, Consumer Dispute Assistance, and...

  1. Design and implementation of a laboratory-based drug design and synthesis advanced pharmacy practice experience.

    PubMed

    Philip, Ashok; Stephens, Mark; Mitchell, Sheila L; Watkins, E Blake

    2015-04-25

    To provide students with an opportunity to participate in medicinal chemistry research within the doctor of pharmacy (PharmD) curriculum. We designed and implemented a 3-course sequence in drug design or drug synthesis for pharmacy students consisting of a 1-month advanced elective followed by two 1-month research advanced pharmacy practice experiences (APPEs). To maximize student involvement, this 3-course sequence was offered to third-year and fourth-year students twice per calendar year. Students were evaluated based on their commitment to the project's success, productivity, and professionalism. Students also evaluated the course sequence using a 14-item course evaluation rubric. Student feedback was overwhelmingly positive. Students found the experience to be a valuable component of their pharmacy curriculum. We successfully designed and implemented a 3-course research sequence that allows PharmD students in the traditional 4-year program to participate in drug design and synthesis research. Students report the sequence enhanced their critical-thinking and problem-solving skills and helped them develop as independent learners. Based on the success achieved with this sequence, efforts are underway to develop research APPEs in other areas of the pharmaceutical sciences.

  2. Design, synthesis and biological evaluation of tetrahydronaphthyridine derivatives as bioavailable CDK4/6 inhibitors for cancer therapy.

    PubMed

    Zha, Chuantao; Deng, Wenjia; Fu, Yan; Tang, Shuai; Lan, Xiaojing; Ye, Yan; Su, Yi; Jiang, Lei; Chen, Yi; Huang, Ying; Ding, Jian; Geng, Meiyu; Huang, Min; Wan, Huixin

    2018-03-25

    CDK4/6 pathway is an attractive chemotherapeutic target for antitumor drug discovery and development. Herein, we reported the structure-based design and synthesis of a series of novel tetrahydronaphthyridine analogues as selective CDK4/6 inhibitors. Compound 5 was identified as a hit and then systematically structure optimization study was conducted. These efforts led to compound 28, which exhibited excellent in vitro potencies against CDK4/6 enzymatic activity with high selectivity over CDK1, and against Colo-205 cell growth. The compound demonstrated favorable in vitro metabolic and robust mice pharmacokinetic properties. In Colo-205 xenograft models, compound 28 showed potent tumor growth inhibition with acceptable toxic effects, which could serve as a novel anticancer agent for further preclinical study. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  3. Design, synthesis, and biological evaluation of combretabenzodiazepines: a novel class of anti-tubulin agents.

    PubMed

    Galli, Ubaldina; Travelli, Cristina; Aprile, Silvio; Arrigoni, Elena; Torretta, Simone; Grosa, Giorgio; Massarotti, Alberto; Sorba, Giovanni; Canonico, Pier Luigi; Genazzani, Armando A; Tron, Gian Cesare

    2015-02-12

    In the present manuscript, starting from the 1,4-benzodiazepin-2-one nucleus, a privileged structure in medicinal chemistry, we have synthesized a novel class of cis-locked combretastatins named combreatabenzodiazepines. They show similar cytotoxic and antitubulin activity compared to combretastatin A-4 in neuroblastoma cells, showing a better pharmacokinetic profile. This class of compounds has therefore the potential for further development as antitubulin agents.

  4. Molecular design of sequence specific DNA alkylating agents.

    PubMed

    Minoshima, Masafumi; Bando, Toshikazu; Shinohara, Ken-ichi; Sugiyama, Hiroshi

    2009-01-01

    Sequence-specific DNA alkylating agents have great interest for novel approach to cancer chemotherapy. We designed the conjugates between pyrrole (Py)-imidazole (Im) polyamides and DNA alkylating chlorambucil moiety possessing at different positions. The sequence-specific DNA alkylation by conjugates was investigated by using high-resolution denaturing polyacrylamide gel electrophoresis (PAGE). The results showed that polyamide chlorambucil conjugates alkylate DNA at flanking adenines in recognition sequences of Py-Im polyamides, however, the reactivities and alkylation sites were influenced by the positions of conjugation. In addition, we synthesized conjugate between Py-Im polyamide and another alkylating agent, 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI). DNA alkylation reactivies by both alkylating polyamides were almost comparable. In contrast, cytotoxicities against cell lines differed greatly. These comparative studies would promote development of appropriate sequence-specific DNA alkylating polyamides against specific cancer cells.

  5. One-pot three-component synthesis of novel heterocyclic steroids as a central antioxidant and anti-inflammatory agents.

    PubMed

    Mohamed, Nadia R; Abdelhalim, Mervat M; Khadrawy, Yasser A; Elmegeed, Gamal A; Abdel-Salam, Omar M E

    2012-11-01

    Oxidative stress and inflammation have been implicated in several neurodegenerative and developmental brain disorders. The present work was devoted to the design and synthesis of novel steroid derivatives bearing promising heterocyclic moiety that would act to reduce neuro-inflammation and oxidative stress in brain. The novel heterocyclic steroids were synthesized and their chemical structures were confirmed by studying their analytical and spectral data. The tested compounds were assayed in the model of neuro-inflammation produced in rats by cerebral lipopolysaccharide injection. The intracerebral administration of bacterial endotoxin resulted in cerebral inflammatory state evidenced by increased malondialdehyde (MDA), decreased reduced glutathione (GSH) level, increased nitric oxide as well as increased acetylcholinesterase (AChE) activity in the brain. Compounds 6, 10, 8b and 13a markedly increased reduced glutathione. Malondialadehyde and nitric oxide levels were reduced to normal values after treatment with all tested compounds. AChE activity was normalized by compound 8b and reduced to below normal values by compounds 10 and 14a. These results are exciting in that these agents might be useful candidates in treatment of cerebral inflammation. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Design, facile synthesis, and evaluation of novel spiro- and pyrazolo[1,5-c]quinazolines as cholinesterase inhibitors: Molecular docking and MM/GBSA studies.

    PubMed

    Gálvez, Jaime; Polo, Stivens; Insuasty, Braulio; Gutiérrez, Margarita; Cáceres, Daniela; Alzate-Morales, Jans H; De-la-Torre, Pedro; Quiroga, Jairo

    2018-03-07

    Given the wide spectrum of biological uses of pyrazolo[1,5-c]quinazoline and spiro-quinazoline derivatives as anticancer, anti-inflammatory analgesic agents, and their therapeutic applications in neurodegenerative disorders, it is compulsory to find easy, efficient, and simple methods to obtain and chemically diversify these families of compounds, thereby improving their biological applications. In this paper, we report the design and eco-friendly two-step synthesis of novel, fused spiro-pyrazolo[1,5-c]quinazoline derivatives as cholinesterase inhibitors. In addition, we studied their protein-ligand interactions via molecular docking and MM/GBSA calculations for a further rational design of more potent inhibitors. In first step, 2-(1H-pyrazol-5-yl)anilines were obtained through microwave (MW) assisted solvent-free/catalyst-free conditions and the second step involved the synthesis of the spiro-pyrazolo[1,5-c]quinazolines by a cyclocondensation reaction between 2-(1H-pyrazol-5-yl)anilines and cyclic ketones, or acetophenones, using stirring at room temperature. The compounds were obtained in high purity, good yields (50-97%), and at varying reaction times. The spiro-compounds were evaluated as acetylcholinesterase and butyrylcholinesterase inhibitors (AChEIs/BuChEIs) respectively, and the most potent compound exhibited a moderate AChE inhibitory activity (5f: IC 50  = 84 μM). Molecular docking studies indicated that the binding mode of the compound 5f share common characteristics with the galantamine/donepezil-AChE complexes. Moreover, free binding energy (ΔG) calculations showed a good agreement with the experimental biological activity values. Our theoretical results indicated that halogen bond interactions could be involved with differential potency of these compounds and provide a new starting point to design novel pyrazolo[1,5-c]quinazolines as new anti-Alzheimer agents. Copyright © 2018. Published by Elsevier Ltd.

  7. Arylhydrazone derivatives of naproxen as new analgesic and anti-inflammatory agents: Design, synthesis and molecular docking studies.

    PubMed

    Azizian, Homa; Mousavi, Zahra; Faraji, Hamidreza; Tajik, Mohammad; Bagherzadeh, Kowsar; Bayat, Peyman; Shafiee, Abbas; Almasirad, Ali

    2016-06-01

    A series of new arylidenehydrazone derivatives of naproxen were synthesized and evaluated for their analgesic and anti-inflammatory activities. Some of the synthesized analogues showed comparable activities when compared against naproxen for their analgesic and anti-inflammatory properties. 2-(6-methoxy-2-naphthyl)-N'-[(pyridine-4-yl)methylene]propanoic acid hydrazide 4j was found to be the most active analgesic agent. 2-(6-methoxy-2-naphthyl)-N'-[4-nitrobenzylidene]propanoic acid hydrazide 4g showed highest anti-inflammatory activity in comparison to the naproxen. Molecular modeling study of the synthesized compounds suggested that the designed molecules were well located and bound to the COX-1 and COX-2 active sites. Compound 4g showed the highest selectivity for COX-2 (RCOX-2/COX-1=1.94) and higher affinity rather than naproxen in COX-2 active site (RCOX-2/naproxen=1.28). Moreover, the structural analyses confirmed that the E-ap rotamer is the preferred structure for the arylidenehydrazone derivatives. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The Role of Intelligent Agents in Advanced Information Systems

    NASA Technical Reports Server (NTRS)

    Kerschberg, Larry

    1999-01-01

    In this presentation we review the current ongoing research within George Mason University's (GMU) Center for Information Systems Integration and Evolution (CISE). We define characteristics of advanced information systems, discuss a family of agents for such systems, and show how GMU's Domain modeling tools and techniques can be used to define a product line Architecture for configuring NASA missions. These concepts can be used to define Advanced Engineering Environments such as those envisioned for NASA's new initiative for intelligent design and synthesis environments.

  9. Materials-by-design: computation, synthesis, and characterization from atoms to structures

    NASA Astrophysics Data System (ADS)

    Yeo, Jingjie; Jung, Gang Seob; Martín-Martínez, Francisco J.; Ling, Shengjie; Gu, Grace X.; Qin, Zhao; Buehler, Markus J.

    2018-05-01

    In the 50 years that succeeded Richard Feynman’s exposition of the idea that there is ‘plenty of room at the bottom’ for manipulating individual atoms for the synthesis and manufacturing processing of materials, the materials-by-design paradigm is being developed gradually through synergistic integration of experimental material synthesis and characterization with predictive computational modeling and optimization. This paper reviews how this paradigm creates the possibility to develop materials according to specific, rational designs from the molecular to the macroscopic scale. We discuss promising techniques in experimental small-scale material synthesis and large-scale fabrication methods to manipulate atomistic or macroscale structures, which can be designed by computational modeling. These include recombinant protein technology to produce peptides and proteins with tailored sequences encoded by recombinant DNA, self-assembly processes induced by conformational transition of proteins, additive manufacturing for designing complex structures, and qualitative and quantitative characterization of materials at different length scales. We describe important material characterization techniques using numerous methods of spectroscopy and microscopy. We detail numerous multi-scale computational modeling techniques that complements these experimental techniques: DFT at the atomistic scale; fully atomistic and coarse-grain molecular dynamics at the molecular to mesoscale; continuum modeling at the macroscale. Additionally, we present case studies that utilize experimental and computational approaches in an integrated manner to broaden our understanding of the properties of two-dimensional materials and materials based on silk and silk-elastin-like proteins.

  10. Prostate Cancer Evaluation: Design, Synthesis, and Evaluation of Novel Enzyme-Activated Proton MRI Contrast Agents

    DTIC Science & Technology

    2007-10-01

    colored plates: ALL DTIC reproductions will be in black and white. 14. ABSTRACT The lacZ gene encoding E . coli beta-gal has already been...interaction, lacZ gene encoding E . coli β-gal has already been recognized as the most commonly used reporter system.[34] However, the well-established...Figure 7 Moreover, we are deeply encouraged by the success on the synthesis of the target molecule M7, as shown in Figure 8. f e d cba OH N

  11. Design, Synthesis, and Evaluation of New Tripeptides as COX-2 Inhibitors.

    PubMed

    Vernieri, Ermelinda; Gomez-Monterrey, Isabel; Milite, Ciro; Grieco, Paolo; Musella, Simona; Bertamino, Alessia; Scognamiglio, Ilaria; Alcaro, Stefano; Artese, Anna; Ortuso, Francesco; Novellino, Ettore; Sala, Marina; Campiglia, Pietro

    2013-01-01

    Cyclooxygenase (COX) is a key enzyme in the biosynthetic pathway leading to the formation of prostaglandins, which are mediators of inflammation. It exists mainly in two isoforms COX-1 and COX-2. The conventional nonsteroidal anti-inflammatory drugs (NSAIDs) have gastrointestinal side effects because they inhibit both isoforms. Recent data demonstrate that the overexpression of these enzymes, and in particular of cyclooxygenases-2, promotes multiple events involved in tumorigenesis; in addition, numerous studies show that the inhibition of cyclooxygenases-2 can delay or prevent certain forms of cancer. Agents that inhibit COX-2 while sparing COX-1 represent a new attractive therapeutic development and offer a new perspective for a further use of COX-2 inhibitors. The present study extends the evaluation of the COX activity to all 20(3) possible natural tripeptide sequences following a rational approach consisting in molecular modeling, synthesis, and biological tests. Based on data obtained from virtual screening, only those peptides with better profile of affinity have been selected and classified into two groups called S and E. Our results suggest that these novel compounds may have potential as structural templates for the design and subsequent development of the new selective COX-2 inhibitors drugs.

  12. Density Control of Multi-Agent Systems with Safety Constraints: A Markov Chain Approach

    NASA Astrophysics Data System (ADS)

    Demirer, Nazli

    systems with a single agent and systems with large number of agents due to the probabilistic nature, where the probability distribution of each agent's state evolves according to a finite-state and discrete-time Markov chain (MC). Hence, designing proper decision control policies requires numerically tractable solution methods for the synthesis of Markov chains. The synthesis problem has the form of a Linear Matrix Inequality Problem (LMI), with LMI formulation of the constraints. To this end, we propose convex necessary and sufficient conditions for safety constraints in Markov chains, which is a novel result in the Markov chain literature. In addition to LMI-based, offline, Markov matrix synthesis method, we also propose a QP-based, online, method to compute a time-varying Markov matrix based on the real-time density feedback. Both problems are convex optimization problems that can be solved in a reliable and tractable way, utilizing existing tools in the literature. A Low Earth Orbit (LEO) swarm simulations are presented to validate the effectiveness of the proposed algorithms. Another problem tackled as a part of this research is the generalization of the density control problem to autonomous mobile agents with two control modes: ON and OFF. Here, each mode consists of a (possibly overlapping) finite set of actions, that is, there exist a set of actions for the ON mode and another set for the OFF mode. We give formulation for a new Markov chain synthesis problem, with additional measurements for the state transitions, where a policy is designed to ensure desired safety and convergence properties for the underlying Markov chain.

  13. Guidance and Navigation Software Architecture Design for the Autonomous Multi-Agent Physically Interacting Spacecraft (AMPHIS) Test Bed

    DTIC Science & Technology

    2006-12-01

    NAVIGATION SOFTWARE ARCHITECTURE DESIGN FOR THE AUTONOMOUS MULTI-AGENT PHYSICALLY INTERACTING SPACECRAFT (AMPHIS) TEST BED by Blake D. Eikenberry...Engineer Degree 4. TITLE AND SUBTITLE Guidance and Navigation Software Architecture Design for the Autonomous Multi- Agent Physically Interacting...iii Approved for public release; distribution is unlimited GUIDANCE AND NAVIGATION SOFTWARE ARCHITECTURE DESIGN FOR THE AUTONOMOUS MULTI

  14. Phthalocyanine Tetraamine Epoxy-Curing Agents

    NASA Technical Reports Server (NTRS)

    Fohlen, G. M.; Achar, B. N.; Parker, J. A.

    1986-01-01

    Tough fire- and chemical-resistant epoxies produced by using metalphthalocyanine tetraamines (MPT's) of copper, cobalt, or nickel as curing agents. Synthesis of MPT's commercially realizable and gives pure compounds with almost 90-percent yield. Synthesis applicable for metals with atomic radii of about 1.35 angstroms, including Cu, Co, Ni, Zn, Fe, Pt, Al, and V. Possible to use metal phthalocyanines to cure epoxy resins in homogeneous reaction.

  15. Synthesis design of artificial magnetic metamaterials using a genetic algorithm.

    PubMed

    Chen, P Y; Chen, C H; Wang, H; Tsai, J H; Ni, W X

    2008-08-18

    In this article, we present a genetic algorithm (GA) as one branch of artificial intelligence (AI) for the optimization-design of the artificial magnetic metamaterial whose structure is automatically generated by computer through the filling element methodology. A representative design example, metamaterials with permeability of negative unity, is investigated and the optimized structures found by the GA are presented. It is also demonstrated that our approach is effective for the synthesis of functional magnetic and electric metamaterials with optimal structures. This GA-based optimization-design technique shows great versatility and applicability in the design of functional metamaterials.

  16. Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.

    PubMed

    Fu, Rong-Geng; Sun, Yuan; Sheng, Wen-Bing; Liao, Duan-Fang

    2017-08-18

    The dominant paradigm in drug discovery is to design ligands with maximum selectivity to act on individual drug targets. With the target-based approach, many new chemical entities have been discovered, developed, and further approved as drugs. However, there are a large number of complex diseases such as cancer that cannot be effectively treated or cured only with one medicine to modulate the biological function of a single target. As simultaneous intervention of two (or multiple) cancer progression relevant targets has shown improved therapeutic efficacy, the innovation of multi-targeted drugs has become a promising and prevailing research topic and numerous multi-targeted anticancer agents are currently at various developmental stages. However, most multi-pharmacophore scaffolds are usually discovered by serendipity or screening, while rational design by combining existing pharmacophore scaffolds remains an enormous challenge. In this review, four types of multi-pharmacophore modes are discussed, and the examples from literature will be used to introduce attractive lead compounds with the capability of simultaneously interfering with different enzyme or signaling pathway of cancer progression, which will reveal the trends and insights to help the design of the next generation multi-targeted anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. On-bead combinatorial synthesis and imaging of chemical exchange saturation transfer magnetic resonance imaging agents to identify factors that influence water exchange.

    PubMed

    Napolitano, Roberta; Soesbe, Todd C; De León-Rodríguez, Luis M; Sherry, A Dean; Udugamasooriya, D Gomika

    2011-08-24

    The sensitivity of magnetic resonance imaging (MRI) contrast agents is highly dependent on the rate of water exchange between the inner sphere of a paramagnetic ion and bulk water. Normally, identifying a paramagnetic complex that has optimal water exchange kinetics is done by synthesizing and testing one compound at a time. We report here a rapid, economical on-bead combinatorial synthesis of a library of imaging agents. Eighty different 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid (DOTA)-tetraamide peptoid derivatives were prepared on beads using a variety of charged, uncharged but polar, hydrophobic, and variably sized primary amines. A single chemical exchange saturation transfer image of the on-bead library easily distinguished those compounds having the most favorable water exchange kinetics. This combinatorial approach will allow rapid screening of libraries of imaging agents to identify the chemical characteristics of a ligand that yield the most sensitive imaging agents. This technique could be automated and readily adapted to other types of MRI or magnetic resonance/positron emission tomography agents as well.

  18. Design of Monoamine Reuptake Inhibitors: SSRIs, SNRIs and NRIs

    NASA Astrophysics Data System (ADS)

    Whitlock, Gavin A.; Andrews, Mark D.; Brown, Alan D.; Fish, Paul V.; Stobie, Alan; Wakenhut, Florian

    This review will detail the medicinal chemistry involved in the design, synthesis and discovery of selective serotonin, noradrenaline reuptake inhibitors and dual serotonin/noradrenaline reuptake inhibitors. In particular, this review will focus exclusively on series and compounds which have been disclosed within the medicinal chemistry literature between January 2000 and June 2008. Background information on previously disclosed clinical agents, such as atomoxetine, milnacipran and reboxetine, is included for comparison purposes with more recently disclosed agents.

  19. Uncaria gambir Roxb. mediated green synthesis of silver nanoparticles using diethanolamine as capping agent

    NASA Astrophysics Data System (ADS)

    Labanni, A.; Zulhadjri; Handayani, D.; Arief, S.

    2018-01-01

    Studies of silver nanoparticles preparation has been developed increasingly due to the wide application in various areas and field, such as medicine, energy, catalysis, and electronic. An environmental-friendly method is needed to fabricate biocompatible silver nanoparticles without producing hazardous materials to the environment. In this study, we synthesized silver nanoparticles by green synthesis method, using leaf extract of gambir (Uncaria gambir Roxb.) as bioreducing agent and aqueous diethanolamine (DEA) solution as capping agents. The AgNO3/DEA molar ratio was varied to investigate the effect of DEA concentration to the properties of silver nanoparticles. The formation of silver nanoparticles was indicated by colour changes to yellowish brown and confirmed by result of UV-Vis spectrophotometer analysis which shown absorption band at 400 to 410 nm. The absorbance was increased to the reaction time of 24 hours, and was decrease by the increasing of DEA concentration in reaction. TEM analysis showed that prepared silver nanoparticles were spherical in shape with diameter of 3,5 - 45,5 nm. The diameter of DEA capped silver nanoparticles was 13 nm, smaller than uncapped silver nanoparticles which was 26 nm It exhibited good stability to time reaction of one month which was potential to be developed in some fields.

  20. Synthesis and in vitro evaluation of bone-seeking superparamagnetic iron oxide nanoparticles as contrast agents for imaging bone metabolic activity.

    PubMed

    Panahifar, Arash; Mahmoudi, Morteza; Doschak, Michael R

    2013-06-12

    In this article, we report the synthesis and in vitro evaluation of a new class of nonionizing bone-targeting contrast agents based on bisphosphonate-conjugated superparamagnetic iron oxide nanoparticles (SPIONs), for use in imaging of bone turnover with magnetic resonance imaging (MRI). Similar to bone-targeting (99m)Technetium medronate, our novel contrast agent uses bisphosphonates to impart bone-seeking properties, but replaces the former radioisotope with nonionizing SPIONs which enables their subsequent detection using MRI. Our reported method is relatively simple, quick and cost-effective and results in BP-SPIONs with a final nanoparticle size of 17 nm under electron microscopy technique (i.e., TEM). In-vitro binding studies of our novel bone tracer have shown selective binding affinity (around 65%) for hydroxyapatite, the principal mineral of bone. Bone-targeting SPIONs offer the potential for use as nonionizing MRI contrast agents capable of imaging dynamic bone turnover, for use in the diagnosis and monitoring of metabolic bone diseases and related bone pathology.

  1. Isoindoline-1,3-dione derivatives targeting cholinesterases: design, synthesis and biological evaluation of potential anti-Alzheimer's agents.

    PubMed

    Guzior, Natalia; Bajda, Marek; Rakoczy, Jurand; Brus, Boris; Gobec, Stanislav; Malawska, Barbara

    2015-04-01

    Alzheimer's disease is a fatal neurodegenerative disorder with a complex etiology. Because the available therapy brings limited benefits, the effective treatment for Alzheimer's disease remains the unmet challenge. Our aim was to develop a new series of donepezil-based compounds endowed with inhibitory properties against cholinesterases and β-amyloid aggregation. We designed the target compounds as dual binding site acetylcholinesterase inhibitors with N-benzylamine moiety interacting with the catalytic site of the enzyme and an isoindoline-1,3-dione fragment interacting with the peripheral anionic site of the enzyme. The results of pharmacological evaluation lead us to identify a compound 3b as the most potent and selective human acetylcholinesterase inhibitor (hAChE IC50=0.361μM). Kinetic studies revealed that 3b inhibited acetylcholinesterase in non-competitive mode. The result of the parallel artificial membrane permeability assay for the blood-brain barrier indicated that the compound 3b would be able to cross the blood-brain barrier and reach its biological targets in the central nervous system. The selected compound 3b represents a potential lead structure for further development of anti-Alzheimer's agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. New agents for prostate cancer.

    PubMed

    Agarwal, N; Di Lorenzo, G; Sonpavde, G; Bellmunt, J

    2014-09-01

    The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging androgen pathway inhibitors include androgen synthesis inhibitors (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone). Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor (ipilimumab). Biologic agents targeting the molecular drivers of disease are also being investigated as single agents, including cabozantinib (Met and VEGFR2 inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite the disappointing results seen from studies evaluating docetaxel in combination with other agents, including GVAX, anti-angiogentic agents (bevacizumab, aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101), the results from the trial evaluating docetaxel in combination with the clusterin antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of discovering new targets, understanding resistance mechanisms, the optimal sequencing and combinations of available agents, as well as biomarkers predictive for benefit. Novel agents targeting bone metastases are being developed following the success of zoledronic acid

  3. The Design of Collectives of Agents to Control Non-Markovian Systems

    NASA Technical Reports Server (NTRS)

    Lawson, John W.; Wolpert, David H.

    2004-01-01

    The Collective Intelligence (COIN) framework concerns the design of collectives of reinforcement-learning agents such that their interaction causes a provided "world" utility function concerning the entire collective to be maximized. Previously, we applied that framework to scenarios involving Markovian dynamics where no re-evolution of the system from counter-factual initial conditions (an often expensive calculation) is permitted. This approach sets the individual utility function of each agent to be both aligned with the world utility, and at the same time, easy for the associated agents to optimize. Here we extend that approach to systems involving non-Markovian dynamics. In computer simulations, we compare our techniques with each other and with conventional "team games". We show whereas in team games performance often degrades badly with time, it steadily improves when our techniques are used. We also investigate situations where the system's dimensionality is effectively reduced. We show that this leads to difficulties in the agents ability to learn. The implication is that learning is a property only of high-enough dimensional systems.

  4. The Design of Collectives of Agents to Control Non-Markovian Systems

    NASA Technical Reports Server (NTRS)

    Lawson, John W.; Wolpert, David H.; Clancy, Daniel (Technical Monitor)

    2002-01-01

    The 'Collective Intelligence' (COIN) framework concerns the design of collectives of reinforcement-learning agents such that their interaction causes a provided 'world' utility function concerning the entire collective to be maximized. Previously, we applied that framework to scenarios involving Markovian dynamics where no re-evolution of the system from counter-factual initial conditions (an often expensive calculation) is permitted. This approach sets the individual utility function of each agent to be both aligned with the world utility, and at the same time, easy for the associated agents to optimize. Here we extend that approach to systems involving non-Markovian dynamics. In computer simulations, we compare our techniques with each other and with conventional-'team games'. We show whereas in team games performance often degrades badly with time, it steadily improves when our techniques are used. We also investigate situations where the system's dimensionality is effectively reduced. We show that this leads to difficulties in the agents' ability to learn. The implication is that 'learning' is a property only of high-enough dimensional systems.

  5. Three amino acid derivatives of valproic acid: design, synthesis, theoretical and experimental evaluation as anticancer agents.

    PubMed

    Luna-Palencia, Gabriela R; Martinez-Ramos, Federico; Vasquez-Moctezuma, Ismael; Fragoso-Vazquez, Manuel Jonathan; Mendieta-Wejebe, Jessica Elena; Padilla-Martínez, Itzia I; Sixto-Lopez, Yudibeth; Mendez-Luna, David; Trujillo-Ferrara, Jose; Meraz-Rios, Marco A; Fonseca-Sabater, Yadira; Correa-Basurto, Jose

    2014-01-01

    Valproic acid (VPA) is extensively used as an anticonvulsive agent and as a treatment for other neurological disorders. It has been shown that VPA exerts an anti-proliferative effect on several types of cancer cells by inhibiting the activity of histone deacetylases (HDACs), which are involved in replication and differentiation processes. However, VPA has some disadvantages, among which are poor water solubility and hepatotoxicity. Therefore, the aim of the present study was to design and synthesize three derivatives of VPA to improve its physicochemical properties and anti-proliferative effects. For this purpose, the amino acids aspartic acid, glutamic acid and proline were added to the molecular structure of VPA. Docking and molecular dynamics simulations were used to determine the mode of recognition of these three derivatives by different conformations of HDAC8. This receptor was used as the specific target because of its high affinity for this type of substrate. The results demonstrate that, compared to VPA, the test compounds bind to different sites on the enzyme and that hydrogen bonds and hydrophobic interactions play key roles in this difference. The IC50 values of the VPA derivatives, experimentally determined using HeLa cells, were in the mM range. This result indicates that the derivatives have greater antiproliferative effects than the parent compound. Hence, these results suggest that these amino acid derivatives may represent a good alternative for anticancer treatment.

  6. Design synthesis and optimization of joined-wing transports

    NASA Technical Reports Server (NTRS)

    Gallman, John W.; Smith, Stephen C.; Kroo, Ilan M.

    1990-01-01

    A computer program for aircraft synthesis using a numerical optimizer was developed to study the application of the joined-wing configuration to transport aircraft. The structural design algorithm included the effects of secondary bending moments to investigate the possibility of tail buckling and to design joined wings resistant to buckling. The structural weight computed using this method was combined with a statistically-based method to obtain realistic estimates of total lifting surface weight and aircraft empty weight. A variety of 'optimum' joined-wing and conventional aircraft designs were compared on the basis of direct operating cost, gross weight, and cruise drag. The most promising joined-wing designs were found to have a joint location at about 70 percent of the wing semispan. The optimum joined-wing transport is shown to save 1.7 percent in direct operating cost and 11 percent in drag for a 2000 nautical mile transport mission.

  7. 1α,25-Dihydroxyvitamin D3-3β-bromoacetate, a potential cancer therapeutic agent: synthesis and molecular mechanism of action

    PubMed Central

    Ray, Rahul; Lambert, James R.

    2011-01-01

    Synthesis of 1α,25-dihydroxyvitamin D3-3β-bromoacetate (1,25(OH)2D3-3-BE), a potential anti-cancer agent is presented. We also report that mechanism of action of 1,25(OH)2D3-3-BE may involve reduction of its catabolism, as evidenced by the reduced and delayed expression of 1α,25-dihydroxyvitamin D3-24-hydroxylase (CYP24) gene in cellular assays. PMID:21392983

  8. Designing and Implementing a Capstone Gerontology Seminar: Synthesis and Action

    ERIC Educational Resources Information Center

    Sasser, Jennifer R.

    2005-01-01

    This paper focuses on the design and implementation of Gerontology: Synthesis and Action, the capstone seminar for the undergraduate and graduate certificate in gerontology program at Marylhurst University, a small, private liberal arts university in the Portland, Oregon metropolitan area. The institutional and programmatic context in which this…

  9. Role of different chelating agent in synthesis of copper doped tin oxide (Cu-SnO2) nanoparticles

    NASA Astrophysics Data System (ADS)

    Saravanakumar, B.; Anusiya, A.; Rani, B. Jansi; Ravi, G.; Yuvakkumar, R.

    2018-05-01

    An attempt was made to synthesis the copper doped tin oxide (Cu-SnO2) nanoparticles by adopting different chelating agents (NaOH, KOH and C2H2O4) by Sol-gel process. The synthesized products were characterized by XRD, Photoluminescence (PL), Infra- Red (FTIR) and SEM analysis. The XRD confirms the formation of Cu-SnO2 shows the maximum peak at 33.8° with lattice plane (101). The PL peak at 361 and 382 nm due to the recombination of electron in conduction band to valence band infers the optical properties. The IR spectra correspond to the peak at 551 and 620 cm-1 attributed to the characteristics peak for Cu-SnO2 nanoparticles. The SEM images for all three Cu-SnO2 nanoparticles formed by three chelating agent (NaOH, KOH and C2H2O4) facilitates the formation mechanism and the chelating agent Oxalic acid results in formation of nano flowers with diverse layers orientated in random direction. Further SEM studies reveal that, the Cu-SnO2 nanoparticles formed by oxalic acid could posses high surface area with large number layered structured enables the better electrochemical properties and its applications.

  10. Substructural controller synthesis

    NASA Technical Reports Server (NTRS)

    Su, Tzu-Jeng; Craig, Roy R., Jr.

    1989-01-01

    A decentralized design procedure which combines substructural synthesis, model reduction, decentralized controller design, subcontroller synthesis, and controller reduction is proposed for the control design of flexible structures. The structure to be controlled is decomposed into several substructures, which are modeled by component mode synthesis methods. For each substructure, a subcontroller is designed by using the linear quadratic optimal control theory. Then, a controller synthesis scheme called Substructural Controller Synthesis (SCS) is used to assemble the subcontrollers into a system controller, which is to be used to control the whole structure.

  11. Design preferences and cognitive styles: experimentation by automated website synthesis.

    PubMed

    Leung, Siu-Wai; Lee, John; Johnson, Chris; Robertson, David

    2012-06-29

    This article aims to demonstrate computational synthesis of Web-based experiments in undertaking experimentation on relationships among the participants' design preference, rationale, and cognitive test performance. The exemplified experiments were computationally synthesised, including the websites as materials, experiment protocols as methods, and cognitive tests as protocol modules. This work also exemplifies the use of a website synthesiser as an essential instrument enabling the participants to explore different possible designs, which were generated on the fly, before selection of preferred designs. The participants were given interactive tree and table generators so that they could explore some different ways of presenting causality information in tables and trees as the visualisation formats. The participants gave their preference ratings for the available designs, as well as their rationale (criteria) for their design decisions. The participants were also asked to take four cognitive tests, which focus on the aspects of visualisation and analogy-making. The relationships among preference ratings, rationale, and the results of cognitive tests were analysed by conservative non-parametric statistics including Wilcoxon test, Krustal-Wallis test, and Kendall correlation. In the test, 41 of the total 64 participants preferred graphical (tree-form) to tabular presentation. Despite the popular preference for graphical presentation, the given tabular presentation was generally rated to be easier than graphical presentation to interpret, especially by those who were scored lower in the visualization and analogy-making tests. This piece of evidence helps generate a hypothesis that design preferences are related to specific cognitive abilities. Without the use of computational synthesis, the experiment setup and scientific results would be impractical to obtain.

  12. Synthesis of structurally diverse benzosuberene analogues and their biological evaluation as anti-cancer agents

    PubMed Central

    Tanpure, Rajendra P.; George, Clinton S.; Strecker, Tracy E.; Devkota, Laxman; Tidmore, Justin K.; Lin, Chen-Ming; Herdman, Christine A.; MacDonough, Matthew T.; Sriram, Madhavi; Chaplin, David J.; Trawick, Mary Lynn; Pinney, Kevin G.

    2014-01-01

    Diversely functionalized, fused aryl-alkyl ring systems hold a prominent position as well-established molecular frameworks for a variety of anti-cancer agents. The benzosuberene (6,7 fused, also referred to as dihydro-5H-benzo[7]annulene and benzocycloheptene) ring system has emerged as a valuable molecular core component for the development of inhibitors of tubulin assembly, which function as antiproliferative anti-cancer agents and, in certain cases, as vascular disrupting agents (VDAs). Both a phenolic-based analogue (known as KGP18, compound 39) and its corresponding amine-based congener (referred to as KGP156, compound 45), which demonstrate strong inhibition of tubulin assembly (low micromolar range) and potent cytotoxicity (picomolar range for KGP18 and nanomolar range for KGP156) are noteworthy examples of such benzosuberene-based compounds. In order to extend the structure-activity relationship (SAR) knowledge base related to benzosuberene anti-cancer agents, a series of eleven analogues (including KGP18) were prepared in which the methoxylation pattern on the pendant aryl ring as well as functional group incorporation on the fused aryl ring were varied. The synthetic approach to these compounds featured a sequential Wittig olefination, reduction, Eaton's reagent-mediated cyclization strategy to achieve the core benzosuberone intermediate, and represented a higher-yielding synthesis of KGP18 (which we prepared previously through a ring-expansion strategy). Incorporation of a fluorine or chlorine atom at the 1-position of the fused aryl ring or replacement of one of the methoxy groups with hydrogen (on the pendant aryl ring of KGP18) led to benzosuberene analogues that were both strongly inhibitory against tubulin assembly (IC50 approximately 1.0 M) and strongly cytotoxic against selected human cancer cell lines (for example, GI50 = 5.47 nM against NCI-H460 cells with fluorobenzosuberene analogue 37). A water-soluble phosphate prodrug salt of KGP18

  13. Synthesis of Pt/rGO catalysts with two different reducing agents and their methanol electrooxidation activity

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

    Vu, Thu Ha Thi, E-mail: ptntd2004@yahoo.fr; Tran, Thanh Thuy Thi, E-mail: tranthithanhthuygl@gmail.com; Le, Hong Ngan Thi

    2016-01-15

    Highlights: • Pt/rGO catalysts were successfully synthesized using either NaBH{sub 4} or ethylene glycol. • Synthesis using NaBH{sub 4} could improve electrocatalytic towards methanol oxidation of Pt/rGO catalyst. • 40%Pt/rGO synthesized using NaBH{sub 4} showed the best electrocatalytic performance. - Abstract: The synthesis processes of Platinum (Pt) on reduced graphene oxide (rGO) catalysts from graphene oxide (GO) using two reducing agents including sodium borohydride and ethylene glycol is reported. Structure and morphology of Pt/rGO catalysts are characterized by X-ray powder diffraction, transmission electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. Electrocatalytic methanol oxidation properties of these catalysts are evaluated bymore » cyclic voltammetry and chronoamperometry. The results show that catalyst synthesized using sodium borohydride has a higher metallic Pt content and an improved catalytic performance in comparison to catalyst synthesized using ethylene glycol. Moreover, effect of Pt loading amount on electrocatalytic methanol oxidation performance of catalysts synthesized using sodium borohydride is systematically investigated. The optimal Pt loading amount on graphene is determined to be 40%.« less

  14. Design and Synthesis of Gold Nanoparticle Contrast Agents for Atherosclerosis Imaging with Computed tomography

    NASA Astrophysics Data System (ADS)

    Chhour, Peter

    Cell tracking offers the opportunity to study migration and localization of cells in vivo, allowing investigations of disease mechanisms and drug efficacy. Monocytes play a key role in the progression of atherosclerotic plaques in the coronary arteries. While x-ray computed tomography (CT) is commonly used to clinically assess coronary plaque burden, cell tracking with CT is mostly unexplored. The establishment of monocyte cell tracking tools would allow for the direct investigation of gene and drug therapies aimed at monocyte recruitment in atherosclerosis. In this thesis, we present the design and optimization of gold nanoparticles as CT contrast agents for cell tracking of monocyte recruitment to atherosclerotic plaques. Gold nanoparticle polymer constructs with controlled localization are evaluated as potential monocyte labels. However, cytotoxic effects were observed at concentrations necessary for cell labeling. Therefore, variations in physical and chemical properties of gold nanoparticles were explored as cell labels for monocyte tracking. Each formulation was screened for effects on cell viability, cell function and uptake in monocytes. The uptake in monocytes revealed a complex relationship with nanoparticle size behavior dependent on the surface ligand used. This led to the selection of an optimal size and coating for monocyte labeling, 11-mercaptoundecanoic acid coated 15 nm gold nanoparticles. This formulation was further investigated for cell viability, function, and uptake with isolated primary monocytes. Moreover, primary monocytes labeled with this formulation were used to observe monocyte recruitment in atherosclerotic mice. Mice with early atherosclerotic plaques received intravenously injections of gold labeled monocytes and their recruitment to plaques were observed over 5 days with CT. Increases in CT attenuation in the plaque and transmission electron microscopy of plaque sections indicated the presence of gold labeled monocytes in the plaque

  15. Ferrocene-pyrimidine conjugates: Synthesis, electrochemistry, physicochemical properties and antiplasmodial activities.

    PubMed

    Chopra, Rakesh; de Kock, Carmen; Smith, Peter; Chibale, Kelly; Singh, Kamaljit

    2015-07-15

    The promise of hybrid antimalarial agents and the precedence set by the antimalarial drug ferroquine prompted us to design ferrocene-pyrimidine conjugates. Herein, we report the synthesis, electrochemistry and anti-plasmodial evaluation of ferrocenyl-pyrimidine conjugates against chloroquine susceptible NF54 strain of the malaria parasite Plasmodium falciparum. Also their physicochemical properties have been studied. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Designing clinical trials to test disease-modifying agents: application to the treatment trials of Alzheimer's disease.

    PubMed

    Xiong, Chengjie; van Belle, Gerald; Miller, J Philip; Morris, John C

    2011-02-01

    Therapeutic trials of disease-modifying agents on Alzheimer's disease (AD) require novel designs and analyses involving switch of treatments for at least a portion of subjects enrolled. Randomized start and randomized withdrawal designs are two examples of such designs. Crucial design parameters such as sample size and the time of treatment switch are important to understand in designing such clinical trials. The purpose of this article is to provide methods to determine sample sizes and time of treatment switch as well as optimum statistical tests of treatment efficacy for clinical trials of disease-modifying agents on AD. A general linear mixed effects model is proposed to test the disease-modifying efficacy of novel therapeutic agents on AD. This model links the longitudinal growth from both the placebo arm and the treatment arm at the time of treatment switch for these in the delayed treatment arm or early withdrawal arm and incorporates the potential correlation on the rate of cognitive change before and after the treatment switch. Sample sizes and the optimum time for treatment switch of such trials as well as optimum test statistic for the treatment efficacy are determined according to the model. Assuming an evenly spaced longitudinal design over a fixed duration, the optimum treatment switching time in a randomized start or a randomized withdrawal trial is half way through the trial. With the optimum test statistic for the treatment efficacy and over a wide spectrum of model parameters, the optimum sample size allocations are fairly close to the simplest design with a sample size ratio of 1:1:1 among the treatment arm, the delayed treatment or early withdrawal arm, and the placebo arm. The application of the proposed methodology to AD provides evidence that much larger sample sizes are required to adequately power disease-modifying trials when compared with those for symptomatic agents, even when the treatment switch time and efficacy test are optimally

  17. On the engineering design for systematic integration of agent-orientation in industrial automation.

    PubMed

    Yu, Liyong; Schüller, Andreas; Epple, Ulrich

    2014-09-01

    In today's automation industry, agent-oriented development of system functionalities appears to have a great potential for increasing autonomy and flexibility of complex operations, while lowering the workload of users. In this paper, we present a reference model for the harmonious and systematical integration of agent-orientation in industrial automation. Considering compatibility with existing automation systems and best practice, this model combines advantages of function block technology, service orientation and native description methods from the automation standard IEC 61131-3. This approach can be applied as a guideline for the engineering design of future agent-oriented automation systems. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

  18. Multifunctional Nanomaterials: Design, Synthesis and Application Properties.

    PubMed

    Martinelli, Marisa; Strumia, Miriam Cristina

    2017-02-07

    The immense scope of variation in dendritic molecules (hyper-branching, nano-sized, hydrophobicity/hydrophilicity, rigidity/flexibility balance, etc.) and their versatile functionalization, with the possibility of multivalent binding, permit the design of highly improved, novel materials. Dendritic-based materials are therefore viable alternatives to conventional polymers. The overall aim of this work is to show the advantages of dendronization processes by presenting the synthesis and characterization of three different dendronized systems: (I) microbeads of functionalized chitosan; (II) nanostructuration of polypropylene surfaces; and (III) smart dendritic nanogels. The particular properties yielded by these systems could only be achieved thanks to the dendronization process.

  19. Systematic process synthesis and design methods for cost effective waste minimization

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

    Biegler, L.T.; Grossman, I.E.; Westerberg, A.W.

    We present progress on our work to develop synthesis methods to aid in the design of cost effective approaches to waste minimization. Work continues to combine the approaches of Douglas and coworkers and of Grossmann and coworkers on a hierarchical approach where bounding information allows it to fit within a mixed integer programming approach. We continue work on the synthesis of reactors and of flexible separation processes. In the first instance, we strive for methods we can use to reduce the production of potential pollutants, while in the second we look for ways to recover and recycle solvents.

  20. ADVANCED MOLECULAR DESIGN OF BIOPOLYMERS FOR TRANSMUCOSAL AND INTRACELLULAR DELIVERY OF CHEMOTHERAPEUTIC AGENTS AND BIOLOGICAL THERAPEUTICS

    PubMed Central

    Liechty, William B.; Caldorera-Moore, Mary; Phillips, Margaret A.; Schoener, Cody; Peppas, Nicholas A.

    2011-01-01

    Hydrogels have been instrumental in the development of polymeric systems for controlled release of therapeutic agents. These materials are attractive for transmucosal and intracellular drug delivery because of their facile synthesis, inherent biocompatibility, tunable physicochemical properties, and capacity to respond to various physiological stimuli. In this contribution, we outline a multifaceted hydrogel-based approach for expanding the range of therapeutics in oral formulations from classical small-molecule drugs to include proteins, chemotherapeutics, and nucleic acids. Through judicious materials selection and careful design of copolymer composition and molecular architecture, we can engineer systems capable of responding to distinct physiological cues, with tunable physicochemical properties that are optimized to load, protect, and deliver valuable macromolecular payloads to their intended site of action. These hydrogel carriers, including complexation hydrogels, tethered hydrogels, interpenetrating networks, nanoscale hydrogels, and hydrogels with decorated structures are investigated for their ability respond to changes in pH, to load and release insulin and fluorescein, and remain non-toxic to Caco-2 cells. Our results suggest these novel hydrogel networks have great potential for controlled delivery of proteins, chemotherapeutics, and nucleic acids. PMID:21699934

  1. The Total Synthesis Problem of linear multivariable control. II - Unity feedback and the design morphism

    NASA Technical Reports Server (NTRS)

    Sain, M. K.; Antsaklis, P. J.; Gejji, R. R.; Wyman, B. F.; Peczkowski, J. L.

    1981-01-01

    Zames (1981) has observed that there is, in general, no 'separation principle' to guarantee optimality of a division between control law design and filtering of plant uncertainty. Peczkowski and Sain (1978) have solved a model matching problem using transfer functions. Taking into consideration this investigation, Peczkowski et al. (1979) proposed the Total Synthesis Problem (TSP), wherein both the command/output-response and command/control-response are to be synthesized, subject to the plant constraint. The TSP concept can be subdivided into a Nominal Design Problem (NDP), which is not dependent upon specific controller structures, and a Feedback Synthesis Problem (FSP), which is. Gejji (1980) found that NDP was characterized in terms of the plant structural matrices and a single, 'good' transfer function matrix. Sain et al. (1981) have extended this NDP work. The present investigation is concerned with a study of FSP for the unity feedback case. NDP, together with feedback synthesis, is understood as a Total Synthesis Problem.

  2. Computational Design of Metal Ion Sequestering Agents

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

    Hay, Benjamin P.; Rapko, Brian M.

    Organic ligands that exhibit a high degree of metal ion recognition are essential precursors for developing separation processes and sensors for metal ions. Since the beginning of the nuclear era, much research has focused on discovering ligands that target specific radionuclides. Members of the Group 1A and 2A cations (e.g., Cs, Sr, Ra) and the f-block metals (actinides and lanthanides) are of primary concern to DOE. Although there has been some success in identifying ligand architectures that exhibit a degree of metal ion recognition, the ability to control binding affinity and selectivity remains a significant challenge. The traditional approach formore » discovering such ligands has involved lengthy programs of organic synthesis and testing that, in the absence of reliable methods for screening compounds before synthesis, have resulted in much wasted research effort. This project seeks to enhance and strengthen the traditional approach through computer-aided design of new and improved host molecules. Accurate electronic structure calculations are coupled with experimental data to provide fundamental information about ligand structure and the nature of metal-donor group interactions (design criteria). This fundamental information then is used in a molecular mechanics model (MM) that helps us rapidly screen proposed ligand architectures and select the best members from a set of potential candidates. By using combinatorial methods, molecule building software has been developed that generates large numbers of candidate architectures for a given set of donor groups. The specific goals of this project are: • further understand the structural and energetic aspects of individual donor group- metal ion interactions and incorporate this information within the MM framework • further develop and evaluate approaches for correlating ligand structure with reactivity toward metal ions, in other words, screening capability • use molecule structure building software to

  3. Revised Study Design for Final Phase of the Change Agent Study. Study of Change Agent Programs: A Working Note.

    ERIC Educational Resources Information Center

    Bass, G.; And Others

    The Rand change agent study was designed to determine the factors for successful implementation and continuation of selected federal programs--the Elementary and Secondary Education Act, Title III, Innovation Projects; ESEA Title VII, Bilingual Projects; Vocational Education Part D, Exemplary Programs; and the Right-to-Read program. This report…

  4. 25 CFR 23.12 - Designated tribal agent for service of notice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Designated tribal agent for service of notice. 23.12 Section 23.12 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT Notice of Involuntary Child Custody Proceedings and Payment for Appointed Counsel in State...

  5. Design and multi-step synthesis of chalcone-polyamine conjugates as potent antiproliferative agents.

    PubMed

    Rioux, Benjamin; Pouget, Christelle; Fidanzi-Dugas, Chloë; Gamond, Aurélie; Laurent, Aurélie; Semaan, Josiane; Pinon, Aline; Champavier, Yves; Léger, David Y; Liagre, Bertrand; Duroux, Jean-Luc; Fagnère, Catherine; Sol, Vincent

    2017-09-15

    The aim of this study is to synthesize chalcone-polyamine conjugates in order to enhance bioavailability and selectivity of chalcone core towards cancer cells, using polyamine-based vectors. 3-hydroxy-3',4,4',5'-tetramethoxychalcone (1) and 3',4,4',5'-tetramethoxychalcone (2) were selected as parent chalcones since they were found to be efficient anti-proliferative agents on various cancer cells. A series of ten chalcone-polyamine conjugates was obtained by reacting carboxychalcones with different polyamine tails. Chalcones 1 and 2 showed a strong cytotoxic activity against two prostatic cancer (PC-3 and DU-145) and two colorectal cancer (HT-29 and HCT-116) cell lines. Then, chalcone-spermine conjugates 7d and 8d were shown to be the most active of the series and could be considered as promising compounds for colon and prostatic cancer adjuvant therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Quinoline derivatives bearing pyrazole moiety: Synthesis and biological evaluation as possible antibacterial and antifungal agents.

    PubMed

    El Shehry, Mohamed F; Ghorab, Mostafa M; Abbas, Samir Y; Fayed, Eman A; Shedid, Said A; Ammar, Yousry A

    2018-01-01

    In an attempt for development of new antimicrobial agents, three series of quinoline derivatives bearing pyrazole moiety have been synthesized. The first series was synthesized through the synthesis of 4-(quinolin-2-yloxy)benzaldehyde and 4-(quinolin-2-yloxy)acetophenone and then treatment with ketone or aldehyde derivatives to afford the corresponding chalcones. Cyclization of the latter chalcones with hydrazine derivatives led to the formation of new pyrazoline derivatives. The second series was synthesized via the synthesis of 2-hydrazinylquinoline and then treatment with formylpyrazoles to afford the corresponding hydrazonyl pyrazole derivatives. The third series was synthesized through the treatment of 2-hydrazinylquinoline with ethoxyethylidene, dithioacetal and arylidene derivatives to afford the corresponding pyrazole derivatives. The synthesized compounds were evaluated for their expected antibacterial and antifungal activities; where, the majority of these compounds showed potent antibacterial and antifungal activities against the tested strains of bacteria and fungi. Pyrazole derivative 13b showed better results when compared with the reference drugs as revealed from their MIC values (0.12-0.98 μg/mL). The pyrazole derivative 13b showed fourfold potency of gentamycin in inhibiting the growth of S. flexneri (MIC 0.12 μg/mL). Also, compound 13b showed fourfold potency of amphotericin B in inhibiting the growth of A. clavatus (MIC 0.49 μg/mL) and C. albicans (MIC 0.12 μg/mL), respectively. The same compound showed twofold potency of gentamycin in inhibiting the growth of P. vulgaris (MIC 0.98 μg/mL), equipotent to the ampicillin and amphotericin B in inhibiting the growth of S. epidermidis (MIC 0.49 μg/mL), A. fumigatus (MIC 0.98 μg/mL), respectively. Thus, these studies suggest that quinoline derivatives bearing pyrazole moiety are interesting scaffolds for the development of novel antibacterial and antifungal agents. Copyright © 2017

  7. Rational drug design and synthesis of molecules targeting the angiotensin II type 1 and type 2 receptors.

    PubMed

    Kellici, Tahsin F; Tzakos, Andreas G; Mavromoustakos, Thomas

    2015-03-02

    The angiotensin II (Ang II) type 1 and type 2 receptors (AT1R and AT2R) orchestrate an array of biological processes that regulate human health. Aberrant function of these receptors triggers pathophysiological responses that can ultimately lead to death. Therefore, it is important to design and synthesize compounds that affect beneficially these two receptors. Cardiovascular disease, which is attributed to the overactivation of the vasoactive peptide hormone Αng II, can now be treated with commercial AT1R antagonists. Herein, recent achievements in rational drug design and synthesis of molecules acting on the two AT receptors are reviewed. Quantitative structure activity relationships (QSAR) and molecular modeling on the two receptors aim to assist the search for new active compounds. As AT1R and AT2R are GPCRs and drug action is localized in the transmembrane region the role of membrane bilayers is exploited. The future perspectives in this field are outlined. Tremendous progress in the field is expected if the two receptors are crystallized, as this will assist the structure based screening of the chemical space and lead to new potent therapeutic agents in cardiovascular and other diseases.

  8. Molecular Medicine: Synthesis and In Vivo Detection of Agents for use in Boron Neutron Capture Therapy. Final Report

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

    Kabalka, G. W.

    2005-06-28

    The primary objective of the project was the development of in vivo methods for the detection and evaluation of tumors in humans. The project was focused on utilizing positron emission tomography (PET) to monitor the distribution and pharamacokinetics of a current boron neutron capture therapy (BNCT) agent, p-boronophenylalanine (BPA) by labeling it with a fluorine-18, a positron emitting isotope. The PET data was then used to develop enhanced treatment planning protocols. The study also involved the synthesis of new tumor selective BNCTagents that could be labeled with radioactive nuclides for the in vivo detection of boron.

  9. Synthesis and biological evaluation of novel 6-hydroxy-benzo[d][1,3]oxathiol-2-one Schiff bases as potential anticancer agents.

    PubMed

    Chazin, Eliza de Lucas; Sanches, Paola de Souza; Lindgren, Eric Brazil; Vellasco Júnior, Walcimar Trindade; Pinto, Laine Celestino; Burbano, Rommel Mario Rodríguez; Yoneda, Julliane Diniz; Leal, Kátia Zaccur; Gomes, Claudia Regina Brandão; Wardell, James Lewis; Wardell, Solange Maria Silva Veloso; Montenegro, Raquel Carvalho; Vasconcelos, Thatyana Rocha Alves

    2015-01-27

    With the aim of discovering new anticancer agents, we have designed and synthesized novel 6-hydroxy-benzo[d][1,3]oxathiol-2-one Schiff bases. The synthesis started with the selective nitration at 5-position of 6-hydroxybenzo[d][1,3]oxathiol-2-one (1) leading to the nitro derivative 2. The nitro group of 2 was reduced to give the amino intermediate 3. Schiff bases 4a-r were obtained from coupling reactions between 3 and various benzaldehydes and heteroaromatic aldehydes. All the new compounds were fully identified and characterized by NMR (1H and 13C) and specifically for 4q by X-ray crystallography. The in vitro cytotoxicity of the compounds was evaluated against cancer cell lines (ACP-03, SKMEL-19 and HCT-116) by using MTT assay. Schiff bases 4b and 4o exhibited promising cytotoxicity against ACP-03 and SKMEL-19, respectively, with IC50 values lower than 5 μM. This class of compounds can be considered as a good starting point for the development of new lead molecules in the fight against cancer.

  10. The Synthesis Approach to Analysing Educational Design Dataset: Application of Three Scaffolds to a Learning by Design Task for Postgraduate Education Students

    ERIC Educational Resources Information Center

    Thompson, Kate; Carvalho, Lucila; Aditomo, Anindito; Dimitriadis, Yannis; Dyke, Gregory; Evans, Michael A.; Khosronejad, Maryam; Martinez-Maldonado, Roberto; Reimann, Peter; Wardak, Dewa

    2015-01-01

    The aims of the Synthesis and Scaffolding Project were to understand: the role of specific scaffolds in relation to the activity of learners, and the activity of learners during a collaborative design task from multiple perspectives, through the collection and analysis of multiple streams of data and the adoption of a synthesis approach to the…

  11. Design, Synthesis, and Evaluation of Novel Ferroquine and Phenylequine Analogues as Potential Antiplasmodial Agents.

    PubMed

    Jacobs, Leon; de Kock, Carmen; de Villiers, Katherine A; Smith, Peter J; Smith, Vincent J; van Otterlo, Willem A L; Blackie, Margaret A L

    2015-12-01

    7-Chloroquinoline-based antimalarial drugs are effective in the inhibition of hemozoin formation in the food vacuole of the Plasmodium parasite, the causative agent of malaria. We synthesized five series of ferroquine (FQ) and phenylequine (PQ) derivatives, which display good in vitro efficacy toward both the chloroquine-sensitive (CQS) NF54 (IC50 : 4.2 nm) and chloroquine-resistant (CQR) Dd2 (IC50 : 33.7 nm) strains of P. falciparum. Several compounds were found to have good inhibitory activity against β-hematin formation in an NP-40 detergent assay, with IC50 values ranging between 10.4 and 19.2 μm. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. The Design of a Multi-Agent NDE Inspection Qualification System

    NASA Astrophysics Data System (ADS)

    McLean, N.; McKenna, J. P.; Gachagan, A.; McArthur, S.; Hayward, G.

    2007-03-01

    A novel Multi-Agent system (MAS) for NDE inspection qualification is being developed to facilitate a scalable environment allowing integration and automation of new and existing inspection qualification tools. This paper discusses the advantages of using a MAS approach to integrate the large number of disparate NDE software tools. The design and implementation of the system architecture is described, including the development of an ontology to describe the NDE domain.

  13. A monofunctional platinum(II)-based anticancer agent from a salicylanilide derivative: Synthesis, antiproliferative activity, and transcription inhibition.

    PubMed

    Wang, Beilei; Wang, Zhigang; Ai, Fujin; Tang, Wai Kin; Zhu, Guangyu

    2015-01-01

    Cationic monofunctional platinum(II)-based anticancer agents with a general formula of cis-[Pt(NH3)2(N-donor)Cl](+) have recently drawn significant attention due to their unique mode of action, distinctive anticancer spectrum, and promising antitumor activity both in vitro and in vivo. Understanding the mechanism of action of novel monofunctional platinum compounds through rational drug design will aid in the further development of active agents. In this study, we synthesized and evaluated a monofunctional platinum-based anticancer agent SA-Pt containing a bulky salicylanilide moiety. The antiproliferative activity of SA-Pt was close to that of cisplatin. Mechanism studies revealed that SA-Pt entered HeLa cells more efficiently than cisplatin, blocked the cell cycle at the S-phase, and induced apoptosis. The compound bound to DNA as effectively as cisplatin, but did not block RNA polymerase II-mediated transcription as strongly as cisplatin, indicating that once the compound formed Pt-DNA lesions, the salicylanilide group was more easily recognized and removed. This study not only enriches the family of monofunctional platinum-based anticancer agents but also guides the design of more potent monofunctional platinum complexes. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Perfluorophenyl Azides: New Applications in Surface Functionalization and Nanomaterial Synthesis

    PubMed Central

    Liu, Li-Hong; Yan, Mingdi

    2010-01-01

    Conspectus A major challenge in materials science is the ongoing search for coupling agents that are readily synthesized, capable of versatile chemistry, able to easily functionalize materials and surfaces, and efficient in covalently linking organic and inorganic entities. A decade ago, we began a research program investigating perfluorophenylazides (PFPAs) as the coupling agents in surface functionalization and nanomaterial synthesis. The p-substituted PFPAs are attractive heterobifunctional coupling agents because of their two distinct and synthetically distinguishable reactive centers: (i) the fluorinated phenylazide, which is capable of forming stable covalent adducts, and (ii) the functional group R, which can be tailored through synthesis. Two approaches have been undertaken for material synthesis and surface functionalization. The first method involves synthesizing PFPA bearing the first molecule or material with a functional linker R, and then attaching the resulting PFPA to the second material by activating the azido group. In the second approach, the material surface is first functionalized with PFPA via functional center R, and coupling of the second molecule or material is achieved with the surface azido groups. In this Account, we review the design and protocols of the two approaches, providing examples in which PFPA derivatives were successfully used in material surface functionalization, ligand conjugation, and the synthesis of hybrid nanomaterials. The methods developed have proved to be general and versatile, and they are applicable to a wide range of materials (especially those that lack reactive functional groups or are difficult to derivatize) and to various substrates of polymers, oxides, carbon materials, and metal films. The coupling chemistry can be initiated by light, heat, and electrons. Patterned structures can be generated by selectively activating the areas of interest. Furthermore, the process is easy to perform, and light activation

  15. Synthesis of calculational methods for design and analysis of radiation shields for nuclear rocket systems

    NASA Technical Reports Server (NTRS)

    Capo, M. A.; Disney, R. K.; Jordan, T. A.; Soltesz, R. G.; Woodsum, H. C.

    1969-01-01

    Eight computer programs make up a nine volume synthesis containing two design methods for nuclear rocket radiation shields. The first design method is appropriate for parametric and preliminary studies, while the second accomplishes the verification of a final nuclear rocket reactor design.

  16. A Buyer Behaviour Framework for the Development and Design of Software Agents in E-Commerce.

    ERIC Educational Resources Information Center

    Sproule, Susan; Archer, Norm

    2000-01-01

    Software agents are computer programs that run in the background and perform tasks autonomously as delegated by the user. This paper blends models from marketing research and findings from the field of decision support systems to build a framework for the design of software agents to support in e-commerce buying applications. (Contains 35…

  17. Fast Synthesis of Gibbsite Nanoplates and Process Optimization using Box-Behnken Experimental Design

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

    Zhang, Xin; Zhang, Xianwen; Graham, Trent R.

    Developing the ability to synthesize compositionally and morphologically well-defined gibbsite particles at the nanoscale with high yield is an ongoing need that has not yet achieved the level of rational design. Here we report optimization of a clean inorganic synthesis route based on statistical experimental design examining the influence of Al(OH)3 gel precursor concentration, pH, and aging time at temperature. At 80 oC, the optimum synthesis conditions of gel concentration at 0.5 M, pH at 9.2, and time at 72 h maximized the reaction yield up to ~87%. The resulting gibbsite product is composed of highly uniform euhedral hexagonal nanoplatesmore » within a basal plane diameter range of 200-400 nm. The independent roles of key system variables in the growth mechanism are considered. On the basis of these optimized experimental conditions, the synthesis procedure, which is both cost-effective and environmentally friendly, has the potential for mass production scale-up of high quality gibbsite material for various fundamental research and industrial applications.« less

  18. Liposome-chaperoned cell-free synthesis for the design of proteoliposomes: Implications for therapeutic delivery.

    PubMed

    Lu, Mei; Zhao, Xiaoyun; Xing, Haonan; Xun, Zhe; Yang, Tianzhi; Cai, Cuifang; Wang, Dongkai; Ding, Pingtian

    2018-04-03

    Cell-free (CF) protein synthesis has emerged as a powerful technique platform for efficient protein production in vitro. Liposomes have been widely studied as therapeutic carriers due to their biocompatibility, biodegradability, low toxicity, flexible surface manipulation, easy preparation, and higher cargo encapsulation capability. However, rapid immune clearance, insufficient targeting capacity, and poor cytoplasmic delivery efficiency substantially restrict their clinical application. The incorporation of functional membrane proteins (MPs) or peptides allows the transfer of biological properties to liposomes and imparts them with improved circulation, increased targeting, and efficient intracellular delivery. Liposome-chaperoned CF synthesis enables production of proteoliposomes in one-step reaction, which not only substantially simplifies the production procedure but also keeps protein functionality intact. Building off these observations, proteoliposomes with integrated MPs represent an excellent candidate for therapeutic delivery. In this review, we describe recent advances in CF synthesis with emphasis on detailing key factors for improving CF expression efficiency. Furthermore, we provide insights into strategies for rational design of proteoliposomal nanodelivery systems via CF synthesis. Liposome-chaperoned CF synthesis has emerged as a powerful approach for the design of recombinant proteoliposomes in one-step reaction. The incorporation of bioactive MPs or peptides into liposomes via CF synthesis can facilitate the development of proteoliposomal nanodelivery systems with improved circulation, increased targeting, and enhanced cellular delivery capacity. Moreover, by adapting lessons learned from natural delivery vehicles, novel bio-inspired proteoliposomes with enhanced delivery properties could be produced in CF systems. In this review, we first give an overview of CF synthesis with focus on enhancing protein expression in liposome-chaperoned CF

  19. A product of independent beta probabilities dose escalation design for dual-agent phase I trials.

    PubMed

    Mander, Adrian P; Sweeting, Michael J

    2015-04-15

    Dual-agent trials are now increasingly common in oncology research, and many proposed dose-escalation designs are available in the statistical literature. Despite this, the translation from statistical design to practical application is slow, as has been highlighted in single-agent phase I trials, where a 3 + 3 rule-based design is often still used. To expedite this process, new dose-escalation designs need to be not only scientifically beneficial but also easy to understand and implement by clinicians. In this paper, we propose a curve-free (nonparametric) design for a dual-agent trial in which the model parameters are the probabilities of toxicity at each of the dose combinations. We show that it is relatively trivial for a clinician's prior beliefs or historical information to be incorporated in the model and updating is fast and computationally simple through the use of conjugate Bayesian inference. Monotonicity is ensured by considering only a set of monotonic contours for the distribution of the maximum tolerated contour, which defines the dose-escalation decision process. Varied experimentation around the contour is achievable, and multiple dose combinations can be recommended to take forward to phase II. Code for R, Stata and Excel are available for implementation. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  20. Synthesis and Preclinical Characterization of a Cationic Iodinated Imaging Contrast Agent (CA4+) and Its Use for Quantitative Computed Tomography of Ex Vivo Human Hip Cartilage.

    PubMed

    Stewart, Rachel C; Patwa, Amit N; Lusic, Hrvoje; Freedman, Jonathan D; Wathier, Michel; Snyder, Brian D; Guermazi, Ali; Grinstaff, Mark W

    2017-07-13

    Contrast agents that go beyond qualitative visualization and enable quantitative assessments of functional tissue performance represent the next generation of clinically useful imaging tools. An optimized and efficient large-scale synthesis of a cationic iodinated contrast agent (CA4+) is described for imaging articular cartilage. Contrast-enhanced CT (CECT) using CA4+ reveals significantly greater agent uptake of CA4+ in articular cartilage compared to that of similar anionic or nonionic agents, and CA4+ uptake follows Donnan equilibrium theory. The CA4+ CECT attenuation obtained from imaging ex vivo human hip cartilage correlates with the glycosaminoglycan content, equilibrium modulus, and coefficient of friction, which are key indicators of cartilage functional performance and osteoarthritis stage. Finally, preliminary toxicity studies in a rat model show no adverse events, and a pharmacokinetics study documents a peak plasma concentration 30 min after dosing, with the agent no longer present in vivo at 96 h via excretion in the urine.

  1. Application of free energy minimization to the design of adaptive multi-agent teams

    NASA Astrophysics Data System (ADS)

    Levchuk, Georgiy; Pattipati, Krishna; Fouse, Adam; Serfaty, Daniel

    2017-05-01

    Many novel DoD missions, from disaster relief to cyber reconnaissance, require teams of humans and machines with diverse capabilities. Current solutions do not account for heterogeneity of agent capabilities, uncertainty of team knowledge, and dynamics of and dependencies between tasks and agent roles, resulting in brittle teams. Most importantly, the state-of-the-art team design solutions are either centralized, imposing role and relation assignment onto agents, or completely distributed, suitable for only homogeneous organizations such as swarms. Centralized design models can't provide insights for team's self-organization, i.e. adapting team structure over time in distributed collaborative manner by team members with diverse expertise and responsibilities. In this paper we present an information-theoretic formalization of team composition and structure adaptation using a minimization of variational free energy. The structure adaptation is obtained in an iterative distributed and collaborative manner without the need for centralized control. We show that our model is lightweight, predictive, and produces team structures that theoretically approximate an optimal policy for team adaptation. Our model also provides a unique coupling between the structure and action policy, and captures three essential processes of learning, perception, and control.

  2. Design, synthesis and biological evaluation of 4'-aminochalcone-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease.

    PubMed

    Xiao, Ganyuan; Li, Yan; Qiang, Xiaoming; Xu, Rui; Zheng, Yunxiaozhu; Cao, Zhongcheng; Luo, Li; Yang, Xia; Sang, Zhipei; Su, Fu; Deng, Yong

    2017-02-01

    A series of 4'-aminochalcone-revastigmine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. The results showed that most of these compounds exhibited good multifunctional activities. In particular, compound 6c displayed the best inhibitory potency on acetylcholinesterase (IC 50 =4.91μM), and significant antioxidative activity with a value 2.83-fold of Trolox. The kinetic analysis of AChE inhibition revealed that 6c showed mixed-type inhibition, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. In addition, 6c inhibited self-induced Aβ 1-42 aggregation and Cu 2+ -induced Aβ 1-42 aggregation by 89.5% and 79.7% at 25μM respectively, as well as acted as a selective monoamine oxidase B inhibitor (IC 50 =0.29μM) and a selective biometal chelator. Furthermore, 6c could cross the blood-brain barrier in vitro. Based on these results, Compound 6c could be considered as a very promising lead compound for Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications.

    PubMed

    Mosayebi, Jalal; Kiyasatfar, Mehdi; Laurent, Sophie

    2017-12-01

    In order to translate nanotechnology into medical practice, magnetic nanoparticles (MNPs) have been presented as a class of non-invasive nanomaterials for numerous biomedical applications. In particular, MNPs have opened a door for simultaneous diagnosis and brisk treatment of diseases in the form of theranostic agents. This review highlights the recent advances in preparation and utilization of MNPs from the synthesis and functionalization steps to the final design consideration in evading the body immune system for therapeutic and diagnostic applications with addressing the most recent examples of the literature in each section. This study provides a conceptual framework of a wide range of synthetic routes classified mainly as wet chemistry, state-of-the-art microfluidic reactors, and biogenic routes, along with the most popular coating materials to stabilize resultant MNPs. Additionally, key aspects of prolonging the half-life of MNPs via overcoming the sequential biological barriers are covered through unraveling the biophysical interactions at the bio-nano interface and giving a set of criteria to efficiently modulate MNPs' physicochemical properties. Furthermore, concepts of passive and active targeting for successful cell internalization, by respectively exploiting the unique properties of cancers and novel targeting ligands are described in detail. Finally, this study extensively covers the recent developments in magnetic drug targeting and hyperthermia as therapeutic applications of MNPs. In addition, multi-modal imaging via fusion of magnetic resonance imaging, and also innovative magnetic particle imaging with other imaging techniques for early diagnosis of diseases are extensively provided. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Thieno[3,2-c]pyran-4-one based novel small molecules: their synthesis, crystal structure analysis and in vitro evaluation as potential anticancer agents.

    PubMed

    Nakhi, Ali; Adepu, Raju; Rambabu, D; Kishore, Ravada; Vanaja, G R; Kalle, Arunasree M; Pal, Manojit

    2012-07-01

    Novel thieno[3,2-c]pyran-4-one based small molecules were designed as potential anticancer agents. Expeditious synthesis of these compounds was carried out via a multi-step sequence consisting of few steps such as Gewald reaction, Sandmeyer type iodination, Sonogashira type coupling followed by iodocyclization and then Pd-mediated various C-C bond forming reactions. The overall strategy involved the construction of thiophene ring followed by the fused pyranone moiety and then functionalization at C-7 position of the resultant thieno[3,2-c]pyran-4-one framework. Some of the compounds synthesized showed selective growth inhibition of cancer cells in vitro among which two compounds for example, 5d and 6c showed IC(50) values in the range of 2.0-2.5 μM. The crystal structure analysis of an active compound along with hydrogen bonding patterns and molecular arrangement present within the molecule is described. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Platinum-based anticancer agents: innovative design strategies and biological perspectives.

    PubMed

    Ho, Yee-Ping; Au-Yeung, Steve C F; To, Kenneth K W

    2003-09-01

    The impact of cisplatin on cancer chemotherapy cannot be denied. Over the past 20 years, much effort has been dedicated to discover new platinum-based anticancer agents that are superior to cisplatin or its analogue, carboplatin. Most structural modifications are based on changing one or both of the ligand types coordinated to platinum. Altering the leaving group can influence tissue and intracellular distribution of the drug, whereas the carrier ligand usually determines the structure of adducts formed with DNA. DNA-Pt adducts produced by cisplatin and many of its classical analogues are almost identical, and would explain their similar patterns of tumor sensitivity and susceptibility to resistance. Recently some highly innovative design strategies have emerged, aimed at overcoming platinum resistance and/or to introduce novel mechanisms of antitumor action. Platinum compounds bearing the 1,2-diaminocyclohexane carrier ligand; and those of multinuclear Pt complexes giving rise to radically different DNA-Pt adducts, have resulted in novel anticancer agents capable of circumventing cisplatin resistance. Other strategies have focused on integrating biologically active ligands with platinum moieties intended to selectively localizing the anticancer properties. With the rapid advance in molecular biology, combined with innovation, it is possible new Pt-based anticancer agents will materialize in the near future. Copyright 2003 Wiley Periodicals, Inc.

  6. Green chemistry synthesis of nano-cuprous oxide.

    PubMed

    Ceja-Romero, L R; Ortega-Arroyo, L; Ortega Rueda de León, J M; López-Andrade, X; Narayanan, J; Aguilar-Méndez, M A; Castaño, V M

    2016-04-01

    Green chemistry and a central composite design, to evaluate the effect of reducing agent, temperature and pH of the reaction, were employed to produce controlled cuprous oxide (Cu2O) nanoparticles. Response surface method of the ultraviolet-visible spectroscopy is allowed to determine the most relevant factors for the size distribution of the nanoCu2O. X-ray diffraction reflections correspond to a cubic structure, with sizes from 31.9 to 104.3 nm. High-resolution transmission electron microscopy reveals that the different shapes depend strongly on the conditions of the green synthesis.

  7. Design, synthesis and biological evaluation of hybrids of β-carboline and salicylic acid as potential anticancer and apoptosis inducing agents

    PubMed Central

    Xu, Qi-Bing; Chen, Xiang-Fan; Feng, Jiao; Miao, Jie-Fei; Liu, Ji; Liu, Feng-Tao; Niu, Bi-Xi; Cai, Jin-Yang; Huang, Chao; Zhang, Yanan; Ling, Yong

    2016-01-01

    A novel series of hybrids (7a-l, 8a-l) from β-carboline and salicylic acid (SA) were designed and synthesized, and their in vitro biological activities were evaluated. Most of the hybrids displayed potent antiproliferative activity against five cancer cell lines in vitro, showing potencies superior to 5-FU and harmine. In particular, compound 8h selectively inhibited proliferation of liver cancer SMMC-7721 cells but not normal liver LO2 cells, and displayed greater inhibitory selectivity than intermediate 5h and SA. 8h also induced cancer cell apoptosis in an Annexin V-FITC/propidium iodide flow cytometry assay, and triggered the mitochondrial/caspase apoptosis by decreasing mitochondrial membrane potential which was associated with up-regulation of Bax, down-regulation of Bcl-2 and activation levels of the caspase cascade in a concentration-dependent manner. Our findings suggest that the β-carboline/SA hybrids may hold greater promise as therapeutic agents for the intervention of human cancers. PMID:27824091

  8. 76 FR 59953 - Designation of Agent To Receive Notification of Claimed Infringement

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-28

    ... for comment. The interim regulations have functioned satisfactorily for many years, but issues have... designation of agent using the online template be required, either annually, every two years, or at some other... at least every two years, but the Office invites comment as to the appropriate time period. As is...

  9. Polyaminoquinoline iron chelators for vectorization of antiproliferative agents: design, synthesis, and validation.

    PubMed

    Corcé, Vincent; Morin, Emmanuelle; Guihéneuf, Solène; Renault, Eric; Renaud, Stéphanie; Cannie, Isabelle; Tripier, Raphaël; Lima, Luís M P; Julienne, Karine; Gouin, Sébastien G; Loréal, Olivier; Deniaud, David; Gaboriau, François

    2012-09-19

    Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 μM. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.

  10. Application of a novel design paradigm to generate general nonpeptide combinatorial templates mimicking beta-turns: synthesis of ligands for melanocortin receptors.

    PubMed

    Webb, Thomas R; Jiang, Luyong; Sviridov, Sergey; Venegas, Ruben E; Vlaskina, Anna V; McGrath, Douglas; Tucker, John; Wang, Jian; Deschenes, Alain; Li, Rongshi

    2007-01-01

    We report the further application of a novel approach to template and ligand design by the synthesis of agonists of the melanocortin receptor. This design method uses the conserved structural data from the three-dimensional conformations of beta-turn peptides to design rigid nonpeptide templates that mimic the orientation of the main chain C-alpha atoms in a peptide beta-turn. We report details on a new synthesis of derivatives of template 1 that are useful for the synthesis of exploratory libraries. The utility of this technique is further exemplified by several iterative rounds of high-throughput synthesis and screening, which result in new partially optimized nonpeptide agonists for several melanocortin receptors.

  11. Evolutionary Agent-based Models to design distributed water management strategies

    NASA Astrophysics Data System (ADS)

    Giuliani, M.; Castelletti, A.; Reed, P. M.

    2012-12-01

    There is growing awareness in the scientific community that the traditional centralized approach to water resources management, as described in much of the water resources literature, provides an ideal optimal solution, which is certainly useful to quantify the best physically achievable performance, but is generally inapplicable. Most real world water resources management problems are indeed characterized by the presence of multiple, distributed and institutionally-independent decision-makers. Multi-Agent Systems provide a potentially more realistic alternative framework to model multiple and self-interested decision-makers in a credible context. Each decision-maker can be represented by an agent who, being self-interested, acts according to local objective functions and produces negative externalities on system level objectives. Different levels of coordination can potentially be included in the framework by designing coordination mechanisms to drive the current decision-making structure toward the global system efficiency. Yet, the identification of effective coordination strategies can be particularly complex in modern institutional contexts and current practice is dependent on largely ad-hoc coordination strategies. In this work we propose a novel Evolutionary Agent-based Modeling (EAM) framework that enables a mapping of fully uncoordinated and centrally coordinated solutions into their relative "many-objective" tradeoffs using multiobjective evolutionary algorithms. Then, by analysing the conflicts between local individual agent and global system level objectives it is possible to more fully understand the causes, consequences, and potential solution strategies for coordination failures. Game-theoretic criteria have value for identifying the most interesting alternatives from a policy making point of view as well as the coordination mechanisms that can be applied to obtain these interesting solutions. The proposed approach is numerically tested on a

  12. Automatic Synthesis of UML Designs from Requirements in an Iterative Process

    NASA Technical Reports Server (NTRS)

    Schumann, Johann; Whittle, Jon; Clancy, Daniel (Technical Monitor)

    2001-01-01

    The Unified Modeling Language (UML) is gaining wide popularity for the design of object-oriented systems. UML combines various object-oriented graphical design notations under one common framework. A major factor for the broad acceptance of UML is that it can be conveniently used in a highly iterative, Use Case (or scenario-based) process (although the process is not a part of UML). Here, the (pre-) requirements for the software are specified rather informally as Use Cases and a set of scenarios. A scenario can be seen as an individual trace of a software artifact. Besides first sketches of a class diagram to illustrate the static system breakdown, scenarios are a favorite way of communication with the customer, because scenarios describe concrete interactions between entities and are thus easy to understand. Scenarios with a high level of detail are often expressed as sequence diagrams. Later in the design and implementation stage (elaboration and implementation phases), a design of the system's behavior is often developed as a set of statecharts. From there (and the full-fledged class diagram), actual code development is started. Current commercial UML tools support this phase by providing code generators for class diagrams and statecharts. In practice, it can be observed that the transition from requirements to design to code is a highly iterative process. In this talk, a set of algorithms is presented which perform reasonable synthesis and transformations between different UML notations (sequence diagrams, Object Constraint Language (OCL) constraints, statecharts). More specifically, we will discuss the following transformations: Statechart synthesis, introduction of hierarchy, consistency of modifications, and "design-debugging".

  13. De novo design and synthesis of ultra-short peptidomimetic antibiotics having dual antimicrobial and anti-inflammatory activities.

    PubMed

    Murugan, Ravichandran N; Jacob, Binu; Ahn, Mija; Hwang, Eunha; Sohn, Hoik; Park, Hyo-Nam; Lee, Eunjung; Seo, Ji-Hyung; Cheong, Chaejoon; Nam, Ky-Youb; Hyun, Jae-Kyung; Jeong, Ki-Woong; Kim, Yangmee; Shin, Song Yub; Bang, Jeong Kyu

    2013-01-01

    Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length) and poor protease stability. In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs) has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(π)- and N(τ)-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti-methicillin-resistant Staphylococcus aureus (MRSA) activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes. The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics.

  14. Substituted 3-((Z)-2-(4-nitrophenyl)-2-(1H-tetrazol-5-yl) vinyl)-4H-chromen-4-ones as novel anti-MRSA agents: synthesis, SAR, and in-vitro assessment.

    PubMed

    Diwakar, Santosh D; Bhagwat, Sachin S; Shingare, Murlidhar S; Gill, Charansing H

    2008-08-15

    In search for a new antibacterial agent with improved antimicrobial spectrum and potency, we designed and synthesized a series of novel 3-((Z)-2-(4-nitrophenyl)-2-(1H-tetrazol-5-yl) vinyl)-4H-chromen-4-ones 7a-h by convergent synthesis approach. All the synthesized compounds were assayed for their in-vitro antibacterial activities against gram-negative and gram-positive bacteria. The preliminary structure-activity relationship, to elucidate the essential structure requirements for the antimicrobial activity that results into anti-MRSA (methicillin-resistant S. aureus) potential, has been described. Amongst the synthesized compounds 7d, 7e, 7f and 7h were found to possess activity against methicillin-resistant S. aureus in addition to the activity against other bacterial strains such as E. faecalis, S. pneumoniae, and E. coli.

  15. Design a Contract: A Simple Principal-Agent Problem as a Classroom Experiment

    ERIC Educational Resources Information Center

    Gachter, Simon; Konigstein, Manfred

    2009-01-01

    The authors present a simple classroom experiment that can be used as a teaching device to introduce important concepts of organizational economics and incentive contracting. First, students take the role of a principal and design a contract that consists of a fixed payment and an incentive component. Second, students take the role of agents and…

  16. Controller design for wind turbine load reduction via multiobjective parameter synthesis

    NASA Astrophysics Data System (ADS)

    Hoffmann, A. F.; Weiβ, F. A.

    2016-09-01

    During the design process for a wind turbine load reduction controller many different, sometimes conflicting requirements must be fulfilled simultaneously. If the requirements can be expressed as mathematical criteria, such a design problem can be solved by a criterion-vector and multi-objective design optimization. The software environment MOPS (Multi-Objective Parameter Synthesis) supports the engineer for such a design optimization. In this paper MOPS is applied to design a multi-objective load reduction controller for the well-known DTU 10 MW reference wind turbine. A significant reduction in the fatigue criteria especially the blade damage can be reached by the use of an additional Individual Pitch Controller (IPC) and an additional tower damper. This reduction is reached as a trade-off with an increase of actuator load.

  17. Software-based high-level synthesis design of FPGA beamformers for synthetic aperture imaging.

    PubMed

    Amaro, Joao; Yiu, Billy Y S; Falcao, Gabriel; Gomes, Marco A C; Yu, Alfred C H

    2015-05-01

    Field-programmable gate arrays (FPGAs) can potentially be configured as beamforming platforms for ultrasound imaging, but a long design time and skilled expertise in hardware programming are typically required. In this article, we present a novel approach to the efficient design of FPGA beamformers for synthetic aperture (SA) imaging via the use of software-based high-level synthesis techniques. Software kernels (coded in OpenCL) were first developed to stage-wise handle SA beamforming operations, and their corresponding FPGA logic circuitry was emulated through a high-level synthesis framework. After design space analysis, the fine-tuned OpenCL kernels were compiled into register transfer level descriptions to configure an FPGA as a beamformer module. The processing performance of this beamformer was assessed through a series of offline emulation experiments that sought to derive beamformed images from SA channel-domain raw data (40-MHz sampling rate, 12 bit resolution). With 128 channels, our FPGA-based SA beamformer can achieve 41 frames per second (fps) processing throughput (3.44 × 10(8) pixels per second for frame size of 256 × 256 pixels) at 31.5 W power consumption (1.30 fps/W power efficiency). It utilized 86.9% of the FPGA fabric and operated at a 196.5 MHz clock frequency (after optimization). Based on these findings, we anticipate that FPGA and high-level synthesis can together foster rapid prototyping of real-time ultrasound processor modules at low power consumption budgets.

  18. A Short Review on the Synthetic Strategies of Duocarmycin Analogs that are Powerful DNA Alkylating Agents.

    PubMed

    Patil, Pravin C; Satam, Vijay; Lee, Moses

    2015-01-01

    The duocarmycins and CC-1065 are members of a class of DNA minor groove, AT-sequence selective, and adenine-N3 alkylating agents, isolated from Streptomyces sp. that exhibit extremely potent cytotoxicity against the growth of cancer cells grown in culture. Initial synthesis and structural modification of the cyclopropa[c] pyrrolo[3,2-e]indole (CPI) DNA-alkylating motif as well as the indole non-covalent binding region in the 1980s have led to several compounds that entered clinical trials as potential anticancer drugs. However, due to significant systemic toxicity none of the analogs have passed clinical evaluation. As a result, the intensity in the design, synthesis, and development of novel analogs of the duocarmycins has continued. Accordingly, in this review, which covers a period from the 1990s through the present time, the design and synthesis of duocarmycin SA are described along with the synthesis of novel and highly cytotoxic analogs that lack the chiral center. Examples of achiral analogs of duocarmycin SA described in this review include seco-DUMSA (39 and 40), seco-amino-CBI-TMI (13, Centanamycin), and seco-hydroxy-CBI-TMI (14). In addition, another novel class of biologically active duocarmycin SA analogs that contained the seco-iso-cyclopropylfurano[2,3-e]indoline (seco-iso-CFI) and seco-cyclopropyltetrahydrofurano[2,3-f]quinoline (seco-CFQ) DNA alkylating submit was also designed and synthesized. The synthesis of seco-iso-CFI-TMI (10, Tafuramycin A) and seco-CFQ-TMI (11, Tafuramycin B) is included in this review.

  19. Synthesis, Characterization and Biological Evaluation of Some Quinoxaline Derivatives: A Promising and Potent New Class of Antitumor and Antimicrobial Agents.

    PubMed

    Al-Marhabi, Aisha R; Abbas, Hebat-Allah S; Ammar, Yousry A

    2015-11-03

    In continuation of our endeavor towards the development of potent and effective anticancer and antimicrobial agents; the present work deals with the synthesis of some novel tetrazolo[1,5-a]quinoxalines, N-pyrazoloquinoxalines, the corresponding Schiff bases, 1,2,4-triazinoquinoxalines and 1,2,4-triazoloquinoxalines. These compounds were synthesized via the reaction of the key intermediate hydrazinoquinoxalines with various reagents and evaluated for anticancer and antimicrobial activity. The results indicated that tetrazolo[1,5-a]quinoxaline derivatives showed the best result, with the highest inhibitory effects towards the three tested tumor cell lines, which were higher than that of the reference doxorubicin and these compounds were non-cytotoxic to normal cells (IC50 values > 100 μg/mL). Also, most of synthesized compounds exhibited the highest degrees of inhibition against the tested strains of Gram positive and negative bacteria, so tetrazolo[1,5-a]quinoxaline derivatives show dual activity as anticancer and antimicrobial agents.

  20. Computer-Aided Structure Based Drug Design Approaches for the Discovery of New Anti-CHIKV Agents.

    PubMed

    Jadav, Surender Singh; Sinha, Barij Nayan; Hilgenfeld, Rolf; Jayaprakash, Venkatesan

    2017-11-10

    Chikungunya is a viral infection caused by Chikungunya virus (CHIKV), an arbovirus transmitted through mosquito (Aedes aegypti and Aedes albopictus) bite. The virus from sylvatic cycle in Africa mutated to new vector adaptation and became one of the major emerging and re-emerging viral infections in the past decade, affecting more than 40 countries. Efforts are being made by many researches to develop means to prevent and control the infection through vaccines and vector control strategy. On the other hand, search for novel chemotherapeutic agents for the treatment of infected patients is on. Approach of repurposed drug is one way of identifying an existing drug for the treatment of CHIKV infection. Review the history of CHIKV nsp2 protease inhibitors derived through structure-based computer-aided drug design along with phytochemicals identified as anti-CHIKV agents. A survey on CHIKV inhibitors reported till date has been carriedout. The data obtained were organized and discussed under natural substances and synthetic derivatives obtained as result of rational design. The review provides a well organized content in chronological order that has highly significant information for medicinal chemist who wish to explore the area of Anti-CHIKV drug design and development. Natural compounds with different scaffolds provides an opportunity to explore Ligand based drug design (LBDD), while rational drug design approaches provides opportunity to explore the Structure based drug design. From the presented mini-review, readers can understand that this area is less explored and has lots of potential in anti-CHIKVviral drug design & development. of reported literature inferred that, unlike other viral proteases, the nsP2 protease can be targeted for CHIKV viral inhibition. The HTVS process for the identification of anti-CHIK agents provided a few successive validated lead compounds against CHIKV infections. Copyright© Bentham Science Publishers; For any queries, please email

  1. Synthesis of 5-thiodidehydropyranylcytosine derivatives as potential anti-HIV agents.

    PubMed

    Yoshimura, Yuichi; Yamazaki, Yoshiko; Saito, Yukako; Natori, Yoshihiro; Imamichi, Tomozumi; Takahata, Hiroki

    2011-06-01

    As a part of our ongoing efforts to identify new anti-HIV agents, a 5'-thiopyrano-nucleoside derivative 4, designed based on 4'-thioD4C 1 and cyclohexenylnucleoside 3, was synthesized. The dihydrothiopyran skeleton of 4 was constructed by the ring closing metathesis of 21 which was synthesized from but-2-yne-1,4-diol. After converting the protecting group from MOM to TBS followed by oxidation, a Pummerer-type thioglycosylation reaction of 24 with persilylated uracil gave the desired 5-thiodihydrothiopyranyluracils 25 and 26 as a mixture of anomers. The conversion of 25 to a cytosine derivative and subsequent deprotection gave a 5-thiodidehydropyranosylcytosine derivative 4 in good yield. The anti-HIV activity of 4 was also evaluated. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Synthesis of dicationic diaryltriazines nucleic acid binding agents

    PubMed Central

    Spychala, J; Wilson, WD; Zhao, M; Tidwell, RR; Dykstra, CC; Hall, JE; Jones, SK; Schinazi, RF

    2010-01-01

    Summary — The synthesis of 2,4-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-1,3,5-triazine 6a and 2,4-bis[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenyl]-1,3,5-triazine 6b in 3 steps from either 4-bromobenzamidine or 4-(carbamoyl)benzamidine is reported. The synthesis of 4,6-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-2-dimethylamino-1,3,5-triazine 9a and 4,6-bis[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenyl]-2-dimethylamino-1,3,5-triazine 9b in 2 steps from 1,4-dicyanobenzene is also described. The compounds 6b and 9b bind strongly to DNA model sequences and inhibit topoisomerase II from 2 microbial sources. Compounds 6a and 9a bind to both DNA and RNA model sequences whereas 6b and 9b essentially do not bind to the RNA model. PMID:21556310

  3. Targeting targeted agents: open issues for clinical trial design.

    PubMed

    Bria, Emilio; Di Maio, Massimo; Carlini, Paolo; Cuppone, Federica; Giannarelli, Diana; Cognetti, Francesco; Milella, Michele

    2009-05-22

    Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources.

  4. Synthesis of the spiroacetal-containing anti-Helicobacter pylori agents CJ-12,954 and CJ-13,014.

    PubMed

    Brimble, Margaret A; Bryant, Christina J

    2006-11-21

    The first synthesis of the spiroacetal-containing anti-Helicobacter pylori agents ent-CJ-12,954 and ent-CJ-13,014 is reported based on the union of a heterocycle-activated spiroacetal-containing sulfone fragment with a phthalide-containing aldehyde fragment; comparison of the 1H and 13C NMR data, optical rotations and HPLC retention times of the synthetic compounds (3S,2"S,5"S,7"S)-(1a) and (3S,2"S,5"R,7"S)-(2a) and the (3R)-diastereomers (3R,2"S,5"S,7"S)-(1b) and (3R,2"S,5"R,7"S)- (2b) with the naturally occurring compounds established that the synthetic isomers (1a) and (2a) were in fact enantiomeric to the natural products CJ-12,954 and CJ-13,014.

  5. Synthesis and characterization of a smart contrast agent sensitive to calcium.

    PubMed

    Dhingra, Kirti; Maier, Martin E; Beyerlein, Michael; Angelovski, Goran; Logothetis, Nikos K

    2008-08-07

    A novel first-generation Ca2+ sensitive contrast agent, Gd-DOPTRA has been synthesized and characterized. The agent shows approximately 100% relaxivity enhancement upon addition of Ca2+. The agent is selective and sensitive to Ca2+ also in the presence of Mg2+ and Zn2+. The relaxivity studies carried out in physiological fluids prove the prospects of the agent for in vivo measurements.

  6. Design and synthesis of chalcone derivatives as potential non-purine xanthine oxidase inhibitors.

    PubMed

    Bui, Trung Huu; Nguyen, Nhan Trung; Dang, Phu Hoang; Nguyen, Hai Xuan; Nguyen, Mai Thanh Thi

    2016-01-01

    Based on some previous research, the chalcone derivatives exhibited potent xanthine oxidase inhibitory activity, e.g. sappanchalcone ( 7 ), with IC 50 value of 3.9 μM, was isolated from Caesalpinia sappan . Therefore, objectives of this research are design and synthesis of 7 and other chalcone derivatives by Claisen-Schmidt condensation and then evaluate their XO inhibitory activity. Fifteen chalcone derivatives were synthesized by Claisen-Schmidt condensation, and were evaluated for XO inhibitory activity. Nine out of 15 synthetic chalcones showed inhibitory activity ( 3 ; 5 - 8 ; 10 - 13 ). Sappanchalcone derivatives ( 11 ) (IC 50 , 2.5 μM) and a novel chalcone ( 13 ) (IC 50 , 2.4 μM) displayed strong xanthine oxidase inhibitory activity that is comparable to allopurinol (IC 50 , 2.5 μM). The structure-activity relationship of these chalcone derivatives was also presented. It is the first research on synthesis sappanchalcone ( 7 ) by Claisen-Schmidt condensation. The overall yield of this procedure was 6.6 %, higher than that of reported procedure (4 %). Design, synthesis, and evaluation of chalcone derivatives were carried out. This result suggests that the chalcone derivative can be used as potential non-purine XO inhibitors.Graphical abstractThe chalcone derivatives as potential non-purine xanthine oxidase inhibitors.

  7. Design and synthesis of an exceptionally stable and highly porous metal-organic framework

    NASA Astrophysics Data System (ADS)

    Li, Hailian; Eddaoudi, Mohamed; O'Keeffe, M.; Yaghi, O. M.

    1999-11-01

    Open metal-organic frameworks are widely regarded as promising materials for applications in catalysis, separation, gas storage and molecular recognition. Compared to conventionally used microporous inorganic materials such as zeolites, these organic structures have the potential for more flexible rational design, through control of the architecture and functionalization of the pores. So far, the inability of these open frameworks to support permanent porosity and to avoid collapsing in the absence of guest molecules, such as solvents, has hindered further progress in the field. Here we report the synthesis of a metal-organic framework which remains crystalline, as evidenced by X-ray single-crystal analyses, and stable when fully desolvated and when heated up to 300°C. This synthesis is achieved by borrowing ideas from metal carboxylate cluster chemistry, where an organic dicarboxylate linker is used in a reaction that gives supertetrahedron clusters when capped with monocarboxylates. The rigid and divergent character of the added linker allows the articulation of the clusters into a three-dimensional framework resulting in a structure with higher apparent surface area and pore volume than most porous crystalline zeolites. This simple and potentially universal design strategy is currently being pursued in the synthesis of new phases and composites, and for gas-storage applications.

  8. The First Total Synthesis of Sporiolide A

    PubMed Central

    Chen, Qi; Linhardt, Robert J.

    2014-01-01

    The first total synthesis of the natural cytotoxic agent sporiolide A has been accomplished from D-glucal in 16 steps with 6.1% overall yield. Carbohydrates were applied as the chiral templates to manipulate the absolute configuration during the synthesis. Pyridinium chlorochromate (PCC)-promoted transformation of the cyclic enol-ether to lactone, followed by Yamaguchi esterification and intramolecular ring closure metathesis, greatly facilitates synthesis of the target compound. PMID:17064018

  9. The first total synthesis of sporiolide A.

    PubMed

    Du, Yuguo; Chen, Qi; Linhardt, Robert J

    2006-10-27

    The first total synthesis of the natural cytotoxic agent sporiolide A has been accomplished from D-glucal in 16 steps with 6.1% overall yield. Carbohydrates were applied as the chiral templates to manipulate the absolute configuration during the synthesis. Pyridinium chlorochromate (PCC)-promoted transformation of the cyclic enol-ether to lactone, followed by Yamaguchi esterification and intramolecular ring closure metathesis, greatly facilitates synthesis of the target compound.

  10. Resolving the Framework Position of Organic Structure-Directing Agents in Hierarchical Zeolites via Polarized Stimulated Raman Scattering.

    PubMed

    Fleury, Guillaume; Steele, Julian A; Gerber, Iann C; Jolibois, F; Puech, P; Muraoka, Koki; Keoh, Sye Hoe; Chaikittisilp, Watcharop; Okubo, Tatsuya; Roeffaers, Maarten B J

    2018-04-05

    The direct synthesis of hierarchically intergrown silicalite-1 can be achieved using a specific diquaternary ammonium agent. However, the location of these molecules in the zeolite framework, which is critical to understand the formation of the material, remains unclear. Where traditional characterization tools have previously failed, herein we use polarized stimulated Raman scattering (SRS) microscopy to resolve molecular organization inside few-micron-sized crystals. Through a combination of experiment and first-principles calculations, our investigation reveals the preferential location of the templating agent inside the linear pores of the MFI framework. Besides illustrating the attractiveness of SRS microscopy in the field of material science to study and spatially resolve local molecular distribution as well as orientation, these results can be exploited in the design of new templating agents for the preparation of hierarchical zeolites.

  11. Reversed enantioselectivity of diisopropyl fluorophosphatase against organophosphorus nerve agents by rational design.

    PubMed

    Melzer, Marco; Chen, Julian C-H; Heidenreich, Anne; Gäb, Jürgen; Koller, Marianne; Kehe, Kai; Blum, Marc-Michael

    2009-12-02

    Diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris is an efficient and robust biocatalyst for the hydrolysis of a range of highly toxic organophosphorus compounds including the nerve agents sarin, soman, and cyclosarin. In contrast to the substrate diisopropyl fluorophosphate (DFP) the nerve agents possess an asymmetric phosphorus atom, which leads to pairs of enantiomers that display markedly different toxicities. Wild-type DFPase prefers the less toxic stereoisomers of the substrates which leads to slower detoxification despite rapid hydrolysis. Enzyme engineering efforts based on rational design yielded two quadruple enzyme mutants with reversed enantioselectivity and overall enhanced activity against tested nerve agents. The reversed stereochemical preference is explained through modeling studies and the crystal structures of the two mutants. Using the engineered mutants in combination with wild-type DFPase leads to significantly enhanced activity and detoxification, which is especially important for personal decontamination. Our findings may also be of relevance for the structurally related enzyme human paraoxonase (PON), which is of considerable interest as a potential catalytic in vivo scavenger in case of organophosphorus poisoning.

  12. Combustion synthesis of LaFeO3 sensing nanomaterial

    NASA Astrophysics Data System (ADS)

    Zaza, F.; Pallozzi, V.; Serra, E.; Pasquali, M.

    2015-06-01

    Since industrial revolution, human activities drive towards unsustainable global economy due to the overexploitation of natural resources and the unacceptable emissions of pollution and greenhouse gases. In order to address that issue, engineering research has been focusing on gas sensors development for monitoring gas emissions and controlling the combustion process sustainability. Semiconductors metal oxides sensors are attractive technology because they require simple design and fabrication, involving high accessibility, small size and low cost. Perovskite oxides are the most promising sensing materials because sensitivity, selectivity, stability and speed-response can be modulated and optimized by changing the chemical composition. One of the most convenient synthesis process of perovskite is the citrate-nitrate auto-combustion method, in which nitrate is the oxidizing agent and citrate is the fuel and the chelating argent in the same time. Since the sensibility of perovskite oxides depends on the defective crystallographic structure and the nanomorphology, the experimental was designed in order to study the dependence of powder properties on the synthesis conditions, such as the solution acidity and the relative amount of metals, nitrates and citric acid. Crystalline structure was studied in depth for defining the effects of synthesis conditions on size, morphology and crystallographic structure of nanopowders of LaFeO3.

  13. Changes in isoprenoid lipid synthesis by gemfibrozil and clofibric acid in rat hepatocytes.

    PubMed

    Hashimoto, F; Taira, S; Hayashi, H

    2000-05-15

    We studied whether gemfibrozil and clofibric acid alter isoprenoid lipid synthesis in rat hepatocytes. After incubation of the cells with the agent for 74 hr, [(14)C]acetate or [(3)H]mevalonate was added, and the cells were further incubated for 4 hr. Gemfibrozil and clofibric acid increased ubiquinone synthesis from [(14)C]acetate and [(3)H]mevalonate. The effect of gemfibrozil was greater than that of clofibric acid. Also, gemfibrozil decreased dolichol synthesis from [(14)C]acetate and [(3)H]mevalonate. However, clofibric acid increased dolichol synthesis from [(3)H]mevalonate. Gemfibrozil decreased cholesterol synthesis from [(14)C]acetate and [(3)H]mevalonate. Clofibric acid decreased cholesterol synthesis from [(14)C]acetate, but did not affect synthesis from [(3)H]mevalonate. These results suggest that both agents, at different rates, activate the synthetic pathway of ubiquinone, at least from mevalonate. Gemfibrozil may inhibit the synthetic pathway of dolichol, at least from mevalonate. Contrary to gemfibrozil, clofibric acid may activate the synthetic pathway of dolichol from mevalonate. Gemfibrozil may inhibit the synthetic pathway of cholesterol from mevalonate in addition to the pathway from acetate to mevalonate inhibited by both agents.

  14. Detection of Alkylating Agents using Electrical and Mechanical Means

    NASA Astrophysics Data System (ADS)

    Gerchikov, Yulia; Borzin, Elena; Gannot, Yair; Shemesh, Ariel; Meltzman, Shai; Hertzog-Ronen, Carmit; Tal, Shay; Stolyarova, Sara; Nemirovsky, Yael; Tessler, Nir; Eichen, Yoav

    2011-08-01

    Alkylating agents are reactive molecules having at least one polar bond between a carbon atom and a good leaving group. These often simple molecules are frequently used in organic synthesis, as sterilizing agents in agriculture and even as anticancer agents in medicine. Unfortunately, for over a century, some of the highly reactive alkylating agents are also being used as blister chemical warfare agents. Being relatively simple to make, the risk is that these will be applied by terrorists as poor people warfare agents. The detection and identification of such alkylating agents is not a simple task because of their high reactivity and simple structure of the reactive site. Here we report on new approaches to the detection and identification of such alkylating agents using electrical (organic field effect transistors) and mechanical (microcantilevers) means.

  15. Synthesis and structure-activity relationship studies of furan-ring fused chalcones as antiproliferative agents.

    PubMed

    Saito, Yusuke; Kishimoto, Maho; Yoshizawa, Yuko; Kawaii, Satoru

    2015-02-01

    As part of our continuing investigation of flavonoid derivatives as potential anticancer substances, the synthesis of 25 cinnamoyl derivatives of benzofuran as furan-fused chalcones was carried-out and these compounds were further evaluated for their antiproliferative activity towards HL60 promyelocytic leukemia cells. In comparison with 2',4'-dihydroxychalcone, attachment of a furan moiety on the A-ring enhanced activity by more than twofold. Benzofurans may be useful in the design of biologically active flavonoids. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. 30 CFR 250.145 - How do I designate an agent or a local agent?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... agent empowered to fulfill your obligations under the Act, the lease, or the regulations in this part... agent empowered to receive notices and submit requests, applications, notices, or supplemental...

  17. Design and Synthesis of Mannich bases as Benzimidazole Derivatives as Analgesic Agents.

    PubMed

    Datar, Prasanna A; Limaye, Saleel A

    2015-01-01

    Mannich bases were selected for 2D QSAR study to derive meaningful relationship between the structural features and analgesic activity. Using the knowledge of important features a novel series was designed to obtain improved analgesic activity. A series of novel Mannich bases 1-(N-substituted amino)methyl]-2-substituted benzimidazole derivatives were synthesized and were screened for analgesic activity. Some of these compounds showed promising analgesic activity when compared with the standard drug diclofenac sodium.

  18. Design, Synthesis and Antitumor Activity of Novel link-bridge and B-Ring Modified Combretastatin A-4 (CA-4) Analogues as Potent Antitubulin Agents

    PubMed Central

    Duan, Yong-Tao; Man, Ruo-Jun; Tang, Dan-Jie; Yao, Yong-Fang; Tao, Xiang-Xiang; Yu, Chen; Liang, Xin-Yi; Makawana, Jigar A.; Zou, Mei-Juan; Wang, Zhong-Chang; Zhu, Hai-Liang

    2016-01-01

    A series of 12 novel acylhydrazone, chalcone and amide–bridged analogues of combretastatin A-4 were designed and synthesized toward tubulin. All these compounds were determined by elemental analysis, 1H NMR, and MS. Among them, compound 7 with acylhydrazone-bridge, bearing a benzyl at the indole-N position, was identified as a potent antiproliferative agent against a panel of cancer cell lines with IC50 values ranging from 0.08 to 35.6 μM. In contrast, its cytotoxic effects on three normal human cells were minimal. Cellular studies have revealed that the induction of apoptosis by compound 7 was associated with a collapse of mitochondrial membrane potential, accumulation of reactive oxygen species, alterations in the expression of some cell cycle-related proteins (Cyclin B1, Cdc25c, Cdc2, P21) and some apoptosis-related proteins (Bax, PARP, Bcl-2, Caspase3). The docking mode showed the binding posture of CA-4 and compound 7 are similar in the colchicine-binding pocket of tubulin, as confirmed by colchicine-tubulin competitive binding assay, tubulin polymerization inhibitory activity, extracellular protein expression determination assay and confocal immunofluorescence microscopy. In vivo study, compound 7 effectively inhibited A549 xenograft tumor growth without causing significant loss of body weight suggesting that compound 7 is a promising new antimitotic agent with clinical potential. PMID:27138035

  19. Simple D-A-D Structural Bisbithiophenyl Diketopyrrolopyrrole (TDPP) as Efficient Bioimaging and Photothermal Agents.

    PubMed

    Zong, Shan; Wang, Xin; Lin, Wenhai; Liu, Shi; Zhang, Wei

    2018-06-20

    Design and synthesis of biocompatible and multi-functional photothermal agents is crucial for effective cancer phototherapy. In order to achieve this ambition, simple D-A-D structural bisbithiophenyl diketopyrrolopyrrole (TDPP) was fabricated. In this molecule, the donor, 2-thiophenylboric acid, was conjugated via Suzuki coupling reaction, which could expand the emission wavelength to the red region of the spectrum. TDPP could self-assemble into stable and uniform nanoparticles (TDPP NPs) in the assistant of amphiphilic Pluronic F-127 polymer. Exposing the TDPP NPs (100 µg/mL) aqueous dispersion to 638 nm (0.61 W/cm2) laser irradiation resulted in a temperature elevation of approximately 30 oC within 5 min, which is high enough for inducing the cytotoxicity and tumor inhibition. Because of the bathochromic shift absorption of TDPP NPs in water, TDPP NPs could also act as a contrast agent for near-infrared fluorescence imaging (NIRF) to visualize the drug distribution in vivo. Coupled with the infrared thermal imaging properties of the photothermal agent, TDPP NPs were proved to be a multifunctional theranostic agent for dual-modal imaging-guided phototherapy.

  20. An Agent-Based Model of New Venture Creation: Conceptual Design for Simulating Entrepreneurship

    NASA Technical Reports Server (NTRS)

    Provance, Mike; Collins, Andrew; Carayannis, Elias

    2012-01-01

    There is a growing debate over the means by which regions can foster the growth of entrepreneurial activity in order to stimulate recovery and growth of their economies. On one side, agglomeration theory suggests the regions grow because of strong clusters that foster knowledge spillover locally; on the other side, the entrepreneurial action camp argues that innovative business models are generated by entrepreneurs with unique market perspectives who draw on knowledge from more distant domains. We will show you the design for a novel agent-based model of new venture creation that will demonstrate the relationship between agglomeration and action. The primary focus of this model is information exchange as the medium for these agent interactions. Our modeling and simulation study proposes to reveal interesting relationships in these perspectives, offer a foundation on which these disparate theories from economics and sociology can find common ground, and expand the use of agent-based modeling into entrepreneurship research.

  1. Design, Synthesis, and Validation of an Effective, Reusable Silicon-Based Transfer Agent for Room-Temperature Pd-Catalyzed Cross-Coupling Reactions of Aryl and Heteroaryl Chlorides with Readily Available Aryl Lithium Reagents

    PubMed Central

    Martinez-Solorio, Dionicio; Melillo, Bruno; Sanchez, Luis; Liang, Yong; Lam, Erwin; Houk, K. N.; Smith, Amos B.

    2016-01-01

    A reusable silicon-based transfer agent (1) has been designed, synthesized, and validated for effective room-temperature palladium-catalyzed cross-coupling reactions (CCRs) of aryl and heteroaryl chlorides with readily accessible aryl lithium reagents. The crystalline, bench-stable siloxane transfer agent (1) is easily prepared via a one-step protocol. Importantly, this “green” CCR protocol circumvents prefunctionalization, isolation of organometallic cross-coupling partners, and/or stoichiometric waste aside from LiCl. DFT calculations support a σ-bond metathesis mechanism during transmetalation and lead to insights on the importance of the CF3 groups. PMID:26835838

  2. Design and Implementation of Context-Aware Musuem Guide Agents

    NASA Astrophysics Data System (ADS)

    Satoh, Ichiro

    This paper presents an agent-based system for building and operating context-aware services in public spaces, including museums. The system provides users with agents and detects the locations of users and deploys location-aware user-assistant agents at computers near the their current locations by using active RFID-tags. When a visitor moves between exhibits in a museum, this dynamically deploys his/her agent at the computers close to the exhibits by using mobile agent technology. It annotates the exhibits in his/her personalized form and navigate him/her user to the next exhibits along his/her routes. It also introduces user movement as a natural approach to interacting between users and agents. To demonstrate the utility and effectiveness of the system, we constructed location/user-aware visitor-guide services and experimented them for two weeks in a public museum.

  3. Design and Synthesis of Novel Phenylpiperazine Derivatives as Potential Anticonvulsant Agents.

    PubMed

    Habib, Monica M W; Abdelfattah, Mohamed A O; Abadi, Ashraf H

    2015-12-01

    Eighteen new 5-benzylidene-3-(4-arylpiperazin-1-ylmethyl)-2-thioxo-imidazolidin-4-ones were designed as hybrid structures from previously reported anticonvulsant compounds, synthesized and tested for anticonvulsant activity. Initial anticonvulsant screening was performed using the strychnine (2 mg/kg IP) potent generalized-induced seizure and pentylenetetrazole (PTZ) (60 mg/kg IP) acute clonic-induced convulsion screens in mice. All the molecules were found to be effective in at least one seizure model, compounds 10, 13, 15, 17, and 18 were active against both types of seizures induced. Compound 13 turned out to be the most active candidate within the strychnine model, having an average survival time of 6 min close to that of the positive control phenytoin, while compound 8 showed 100% protection from the induced PTZ seizures, resembling the protection of the positive control phenobarbital. Initial SAR studies for anticonvulsant activity are discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Design, synthesis, and biological evaluation of oxindole derivatives as antidepressive agents.

    PubMed

    Suthar, Sharad Kumar; Bansal, Sumit; Alam, Md Maqusood; Jaiswal, Varun; Tiwari, Amit; Chaudhary, Anil; Alex, Angel Treasa; Joseph, Alex

    2015-11-15

    The 3-substituted oxindole derivatives were designed, synthesized, and evaluated for antidepressant activity by employing forced swimming test, tail suspension test, and MAO-A inhibition assay. Results of biological studies revealed that the majority of compounds exhibited potent to moderately potent activity and among them, 12 displayed potency comparable to that of the imipramine with %DID of 37.95 and 44.84 in the FST and TST, respectively. At the same time, imipramine showed %DID of 43.62 and 50.64 in the FST and TST, correspondingly. In the MAO-A inhibition assay, 12 showed an IC50 of 18.27 μmol, whereas the reference drug moclobemide displayed an IC50 of 13.1 μmol. The SAR study disclosed that the presence of bromo atom at the phenyl/furanyl or thienyl moiety in the oxindole derivatives was critical for the antidepressant activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. De Novo Design and Synthesis of Ultra-Short Peptidomimetic Antibiotics Having Dual Antimicrobial and Anti-Inflammatory Activities

    PubMed Central

    Ahn, Mija; Hwang, Eunha; Sohn, Hoik; Park, Hyo-Nam; Lee, Eunjung; Seo, Ji-Hyung; Cheong, Chaejoon; Nam, Ky-Youb; Hyun, Jae-Kyung; Jeong, Ki-Woong; Kim, Yangmee; Shin, Song Yub; Bang, Jeong Kyu

    2013-01-01

    Background Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length) and poor protease stability. Methodology/Principal Findings In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs) has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(π)- and N(τ)-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti–methicillin-resistant Staphylococcus aureus (MRSA) activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes. Conclusion/Significance The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics. PMID:24302996

  6. Synthesis and biological studies of positron-emitting radiopharmaceuticals

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

    Dischino, D.D.

    The development and clinical evaluation of two-positron emitting radiopharmaceuticals designed to image myelin in humans is reported. Carbon-11-labeled benzyl methyl ether was synthesized by the reaction of carbon-11-labeled methanol and benzyl chloride in dimethyl sulfoxide containing powdered potassium hydroxide in a radiochemical yield of 43% and a synthesis and purification time of 40 minutes. Carbon-11-labeled diphenylmethanol was synthesized by the reaction of carbon-11-labeled carbon dioxide and phenyllithium followed by the reduction of the carbon-11-labeled intermediate to diphenylmethanol via lithium aluminum hydride in a radiochemical yield of 71% and a synthesis and purification time of 38 minutes. Carbon-11-labeled benzyl methyl ethermore » and diphenylmethanol were each evaluated as myelin imaging agents in three patients with multiple sclerosis via positron-emission tomography. In two out of three patients studied with carbon-11-labeled benzyl methyl ether, the distribution of activity in the brain was not consistent with local lipid content. A new synthesis of carbon-11-labeled-DL-phenylalanine labeled in the benzylic position and the synthesis of fluorine-18-labeled 1-(2-nitro-1-imidazolyl)-3-fluoro-2-propanol, a potential in vivo marker of hypoxic tissue, are reported.« less

  7. Perspective: Toward "synthesis by design": Exploring atomic correlations during inorganic materials synthesis

    NASA Astrophysics Data System (ADS)

    Soderholm, L.; Mitchell, J. F.

    2016-05-01

    Synthesis of inorganic extended solids is a critical starting point from which real-world functional materials and their consequent technologies originate. However, unlike the rich mechanistic foundation of organic synthesis, with its underlying rules of assembly (e.g., functional groups and their reactivities), the synthesis of inorganic materials lacks an underpinning of such robust organizing principles. In the latter case, any such rules must account for the diversity of chemical species and bonding motifs inherent to inorganic materials and the potential impact of mass transport on kinetics, among other considerations. Without such assembly rules, there is less understanding, less predictive power, and ultimately less control of properties. Despite such hurdles, developing a mechanistic understanding for synthesis of inorganic extended solids would dramatically impact the range of new material discoveries and resulting new functionalities, warranting a broad call to explore what is possible. Here we discuss our recent approaches toward a mechanistic framework for the synthesis of bulk inorganic extended solids, in which either embryonic atomic correlations or fully developed phases in solutions or melts can be identified and tracked during product selection and crystallization. The approach hinges on the application of high-energy x-rays, with their penetrating power and large Q-range, to explore reaction pathways in situ. We illustrate this process using two examples: directed assembly of Zr clusters in aqueous solution and total phase awareness during crystallization from K-Cu-S melts. These examples provide a glimpse of what we see as a larger vision, in which large scale simulations, data-driven science, and in situ studies of atomic correlations combine to accelerate materials discovery and synthesis, based on the assembly of well-defined, prenucleated atomic correlations.

  8. Zeolite-like metal–organic frameworks (ZMOFs): Design, synthesis, and properties

    DOE PAGES

    Eddaoudi, Mohamed; Sava, Dorina F.; Eubank, Jarrod F.; ...

    2015-10-24

    This study highlights various design and synthesis approaches toward the construction of ZMOFs, which are metal–organic frameworks (MOFs) with topologies and, in some cases, features akin to traditional inorganic zeolites. The interest in this unique subset of MOFs is correlated with their exceptional characteristics arising from the periodic pore systems and distinctive cage-like cavities, in conjunction with modular intra- and/or extra-framework components, which ultimately allow for tailoring of the pore size, pore shape, and properties towards specific applications.

  9. Design, synthesis, and in vitro evaluation of new amphiphilic cyclodextrin-based nanoparticles for the incorporation and controlled release of acyclovir.

    PubMed

    Perret, Florent; Duffour, Marine; Chevalier, Yves; Parrot-Lopez, Hélène

    2013-01-01

    Acyclovir possesses low solubility in water and in lipid bilayers, so that its dosage forms do not allow suitable drug levels at target sites following oral, local, or parenteral administration. In order to improve this lack of solubility, new cyclodextrin-based amphiphilic derivatives have been designed to form nanoparticles, allowing the efficient encapsulation of this hydrophobic antiviral agent. The present work first describes the synthesis and characterization of five new O-2,O-3 permethylated O-6 alkylthio- and perfluoroalkyl-propanethio-amphiphilic β-cyclodextrins. These derivatives have been obtained with good overall yields. The capacity of these molecules to form nanoparticles in water and to encapsulate acyclovir has then been studied. The nanoparticles prepared from the new β-cyclodextrin derivatives have been characterized by dynamic light scattering and have an average size of 120nm for the fluorinated derivatives and 220nm for the hydrogenated analogs. They all allowed high loading and sustained release of acyclovir. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Story-Based Pedagogical Agents: A Scaffolding Design Approach for the Process of Historical Inquiry in a Web-Based Self-Learning Environment

    ERIC Educational Resources Information Center

    Fujimoto, Toru

    2010-01-01

    The purpose of this research was to design and evaluate a web-based self-learning environment for historical inquiry embedded with different types of instructional support featuring story-based pedagogical agents. This research focused on designing a learning environment by integrating story-based instruction and pedagogical agents as a means to…

  11. Multimodal nanoparticle imaging agents: design and applications

    NASA Astrophysics Data System (ADS)

    Burke, Benjamin P.; Cawthorne, Christopher; Archibald, Stephen J.

    2017-10-01

    Molecular imaging, where the location of molecules or nanoscale constructs can be tracked in the body to report on disease or biochemical processes, is rapidly expanding to include combined modality or multimodal imaging. No single imaging technique can offer the optimum combination of properties (e.g. resolution, sensitivity, cost, availability). The rapid technological advances in hardware to scan patients, and software to process and fuse images, are pushing the boundaries of novel medical imaging approaches, and hand-in-hand with this is the requirement for advanced and specific multimodal imaging agents. These agents can be detected using a selection from radioisotope, magnetic resonance and optical imaging, among others. Nanoparticles offer great scope in this area as they lend themselves, via facile modification procedures, to act as multifunctional constructs. They have relevance as therapeutics and drug delivery agents that can be tracked by molecular imaging techniques with the particular development of applications in optically guided surgery and as radiosensitizers. There has been a huge amount of research work to produce nanoconstructs for imaging, and the parameters for successful clinical translation and validation of therapeutic applications are now becoming much better understood. It is an exciting time of progress for these agents as their potential is closer to being realized with translation into the clinic. The coming 5-10 years will be critical, as we will see if the predicted improvement in clinical outcomes becomes a reality. Some of the latest advances in combination modality agents are selected and the progression pathway to clinical trials analysed. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

  12. Bubble template synthesis of hollow gold nanoparticles and their applications as theranostic agents

    NASA Astrophysics Data System (ADS)

    Huang, Chienwen

    Hollow gold nanoparticle with a sub-30nm polycrystalline shell and a 50 nm hollow core has been successfully synthesized through the reduction of sodium gold sulfite by electrochemically evolved hydrogen. Such hollow gold nanoparticles exhibit unique plasmonic properties. They strongly scatter and absorb near infrared light. In this thesis we seek to understand the formation mechanism of hollow gold nanoparticles in this new synthesis process and their plasmonic properties. Also, we explore their biomedical applications as theranostic agents (therapeutic and diagnostic imaging). A lithographically patterned electrode consisting of Ag stripes on a glass substrate was used to investigate the formation process of hollow gold nanoparticles. Ag stripes served as working electrode for electrochemically evolution of hydrogen, and adjacent glass areas provided supporting surface for hydrogen nanobubbles nucleation and growth. Hydrogen nanobubbles served as both templates and reducing agents to trigger the autocatalytic disproportionation reaction of sodium gold sulfite. The effects of applied potential and the additives in the electrolyte have been studied. It has been found that the size and size distribution of hollow gold nanoparticle are directly relative to the applied potential, i.e. the hydrogen evolution rate. It has also been found the addition of Ni2+ ions can greatly improve the size distribution of hollow gold nanoparticles that can be contributed to that the newly electrodeposited nickel metal can enhance the hydrogen evolution efficiency. Another additive, ethylenediamine (EDA) can suppress the autocatalytic reaction of gold sulfite to increase the stability of sodium gold sulfite electrolyte. To capture such electrochemically evolved hydrogen nanobubbles, and subsequently to generate hollow gold nanoparticles in large numbers, alumina membranes were placed on the top of the working electrode. Anodic alumina membrane consists of ~200 nm pores, which provides

  13. Combustion synthesis of LaFeO{sub 3} sensing nanomaterial

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

    Zaza, F., E-mail: fabio.zaza@enea.it; Serra, E.; Pallozzi, V.

    2015-06-23

    Since industrial revolution, human activities drive towards unsustainable global economy due to the overexploitation of natural resources and the unacceptable emissions of pollution and greenhouse gases. In order to address that issue, engineering research has been focusing on gas sensors development for monitoring gas emissions and controlling the combustion process sustainability. Semiconductors metal oxides sensors are attractive technology because they require simple design and fabrication, involving high accessibility, small size and low cost. Perovskite oxides are the most promising sensing materials because sensitivity, selectivity, stability and speed-response can be modulated and optimized by changing the chemical composition. One of themore » most convenient synthesis process of perovskite is the citrate-nitrate auto-combustion method, in which nitrate is the oxidizing agent and citrate is the fuel and the chelating argent in the same time. Since the sensibility of perovskite oxides depends on the defective crystallographic structure and the nanomorphology, the experimental was designed in order to study the dependence of powder properties on the synthesis conditions, such as the solution acidity and the relative amount of metals, nitrates and citric acid. Crystalline structure was studied in depth for defining the effects of synthesis conditions on size, morphology and crystallographic structure of nanopowders of LaFeO{sub 3}.« less

  14. Design, synthesis and docking studies of novel 1,2-dihydro-4-hydroxy-2-oxoquinoline-3-carboxamide derivatives as a potential anti-proliferative agents.

    PubMed

    Banu, Saleha; Bollu, Rajitha; Bantu, Rajashaker; Nagarapu, Lingaiah; Polepalli, Sowjanya; Jain, Nishant; Vangala, Radhika; Manga, Vijjulatha

    2017-01-05

    A new series of 4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide hybrids 8a-l have been designed and synthesized using peptide coupling agents with substituted N-phenyl piperazines and piperidines with good to excellent yields. The synthesized compounds were evaluated for their in vitro anti-proliferative activity against PANC 1, HeLa and MDA-MB-231. The compounds 8d, 8e, 8f, 8g, 8h and 8k exhibited considerable anti-proliferative activity with GI 50 values ranging from 0.15 to 1.4 μM. The structure and anti-proliferative activity relationship was further supported by in silico molecular docking study of the active compounds against tubulin protein. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Cyclohexa-2,5-diene-1,4-dione-based antiproliferative agents: design, synthesis, and cytotoxic evaluation.

    PubMed

    Petronzi, Carmen; Festa, Michela; Peduto, Antonella; Castellano, Maria; Marinello, Jessica; Massa, Antonio; Capasso, Anna; Capranico, Giovanni; La Gatta, Annalisa; De Rosa, Mario; Caraglia, Michele; Filosa, Rosanna

    2013-04-30

    Tumors are diseases characterized by uncontrolled cell growth and, in spite of the progress of medicine over the years, continue to represent a major threat to the health, requiring new therapies. Several synthetic compounds, such as those derived from natural sources, have been identified as anticancer drugs; among these compounds quinone represent the second largest class of anticancer agents in use. Several studies have shown that these act on tumor cells through several mechanisms. An important objective of this work is to develop quinoidscompounds showing antitumor activity, but with fewer side effects. The parachinone cannabinol HU-331, is a small molecule that with its core 4-hydroxy-1,4-benzoquinone, exhibits a potent and selective cytotoxic activity on different tumor cell lines. A series of derivatives 3-hydroxy-1,4-benzochinoni were thus developed through HU-331 chemical modifications. The purpose of the work is to test the ability of the compounds to induce proliferative inhibition and study the mechanisms of cell death. The antitumor activities were evaluated in vitro by examining their cytotoxic effects against different human cancer cell lines. All cell lines tested were plated in 96-multiwell and treated with HU-100-V at different concentrations and cell viability was evaluated byMTT assay. Subsequently via flow cytometry (FACS) it was possible to assess apoptosis by the system of double labeling with PI and Annexin-V, and the effect of the compounds on ROS formation by measuring the dichlorofluorescein fluorescence. The substitution by n-hexyl chain considerably enhanced the bioactivity of the compounds. In details, 2-hexyl-5-hydroxycyclohexa-2,5-diene-1,4-dione (V), 2,5-Dimethoxy-3-hexyl-2,5-cyclohexadiene-1,4-dione (XII) and 2-hydroxy-5-methoxy-3-hexyl-cyclohexa-2,5-diene-1,4-dione (XIII) showed most prominent cytotoxicity against almost human tumour cell lines. Compound V was further subjected to downstream apoptotic analysis, demostrating a

  16. Synthesis and biological activity of mustard derivatives of thymine.

    PubMed

    Hadj-Bouazza, Amel; Teste, Karine; Colombeau, Ludovic; Chaleix, Vincent; Zerrouki, Rachida; Kraemer, Michel; Sainte Catherine, Odile

    2008-05-01

    The synthesis and biological activity of a novel DNA cross-linking antitumor agent is presented. The new alkylating agent significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line.

  17. Design, Specification, and Synthesis of Aircraft Electric Power Systems Control Logic

    NASA Astrophysics Data System (ADS)

    Xu, Huan

    Cyber-physical systems integrate computation, networking, and physical processes. Substantial research challenges exist in the design and verification of such large-scale, distributed sensing, actuation, and control systems. Rapidly improving technology and recent advances in control theory, networked systems, and computer science give us the opportunity to drastically improve our approach to integrated flow of information and cooperative behavior. Current systems rely on text-based specifications and manual design. Using new technology advances, we can create easier, more efficient, and cheaper ways of developing these control systems. This thesis will focus on design considerations for system topologies, ways to formally and automatically specify requirements, and methods to synthesize reactive control protocols, all within the context of an aircraft electric power system as a representative application area. This thesis consists of three complementary parts: synthesis, specification, and design. The first section focuses on the synthesis of central and distributed reactive controllers for an aircraft elec- tric power system. This approach incorporates methodologies from computer science and control. The resulting controllers are correct by construction with respect to system requirements, which are formulated using the specification language of linear temporal logic (LTL). The second section addresses how to formally specify requirements and introduces a domain-specific language for electric power systems. A software tool automatically converts high-level requirements into LTL and synthesizes a controller. The final sections focus on design space exploration. A design methodology is proposed that uses mixed-integer linear programming to obtain candidate topologies, which are then used to synthesize controllers. The discrete-time control logic is then verified in real-time by two methods: hardware and simulation. Finally, the problem of partial observability and

  18. Design and Synthesis of Bifunctional Oxime Reactivators of OP- inhibited Cholinesterase

    DTIC Science & Technology

    2013-08-01

    was introduce the 2- aldehyde as a nitrile via the pyridine N-oxide. Another approach (II), was to simply perform 2- hydoxymethylation of pyridines...original design plan called for introducing an aldehyde that could be coupled to various amines and diamines through reductive amination. Interestingly...chromatography DCM: MeOH (90:10) as a yellow oil. Synthesis of 37 (Oxime formation general procedure) To the ketone 36 (340 mg, 1,123 mmol) in 1

  19. Agent Technologies Designed to Facilitate Interactive Knowledge Construction

    ERIC Educational Resources Information Center

    Graesser, Arthur C.; Jeon, Moongee; Dufty, David

    2008-01-01

    During the last decade, interdisciplinary researchers have developed technologies with animated pedagogical agents that interact with the student in language and other communication channels (such as facial expressions and gestures). These pedagogical agents model good learning strategies and coach the students in actively constructing knowledge…

  20. DNA synthesis security.

    PubMed

    Nouri, Ali; Chyba, Christopher F

    2012-01-01

    It is generally assumed that genetic engineering advances will, inevitably, facilitate the misapplication of biotechnology toward the production of biological weapons. Unexpectedly, however, some of these very advances in the areas of DNA synthesis and sequencing may enable the implementation of automated and nonintrusive safeguards to avert the illicit applications of biotechnology. In the case of DNA synthesis, automated DNA screening tools could be built into DNA synthesizers in order to block the synthesis of hazardous agents. In addition, a comprehensive safety and security regime for dual-use genetic engineering research could include nonintrusive monitoring of DNA sequencing. This is increasingly feasible as laboratories outsource this service to just a few centralized sequencing factories. The adoption of automated, nonintrusive monitoring and surveillance of the DNA synthesis and sequencing pipelines may avert many risks associated with dual-use biotechnology. Here, we describe the historical background and current challenges associated with dual-use biotechnologies and propose strategies to address these challenges.

  1. Design, Synthesis, and Structure--Activity Relationship of New 2-Aryl-3,4-dihydro-β-carbolin-2-ium Salts as Antifungal Agents.

    PubMed

    Hou, Zhe; Zhu, Li-Fei; Yu, Xin-chi; Sun, Ma-Qiang; Miao, Fang; Zhou, Le

    2016-04-13

    Twenty-two 2-aryl-9-methyl-3,4-dihydro-β-carbolin-2-ium bromides along with four 9-demethylated derivatives were synthesized and characterized by spectroscopic analysis. By using the mycelium growth rate method, the compounds were evaluated for antifungal activities in vitro against six plant pathogenic fungi, and structure-activity relationships (SAR) were derived. Almost all of the compounds showed obvious inhibition activity on each of the fungi at 150 μM. For all of the fungi, 10 of the compounds showed average inhibition rates of >80% at 150 μM, and most of their EC50 values were in the range of 2.0-30.0 μM. SAR analysis showed that the substitution pattern of the N-aryl ring significantly influences the activity; N9-alkylation improves the activity, whereas aromatization of ring-C reduces the activity. It was concluded that the present research provided a series of new 2-aryl-9-alkyl-3,4-dihydro-β-carbolin-2-iums with excellent antifungal potency and structure optimization design for the development of new carboline antifungal agents.

  2. Computational Design of Metal Ion Sequestering Agents

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

    Hay, Benjamin P.; Rapko, Brian M.

    Organic ligands that exhibit a high degree of metal ion recognition are essential precursors for developing separation processes and sensors for metal ions. Since the beginning of the nuclear era, much research has focused on discovering ligands that target specific radionuclides. Members of the Group 1A and 2A cations (e.g., Cs, Sr, Ra) and the f-block metals (actinides and lanthanides) are of primary concern to DOE. Although there has been some success in identifying ligand architectures that exhibit a degree of metal ion recognition, the ability to control binding affinity and selectivity remains a significant challenge. The traditional approach formore » discovering such ligands has involved lengthy programs of organic synthesis and testing that, in the absence of reliable methods for screening compounds before synthesis, have resulted in much wasted research effort.« less

  3. Versatile synthesis and rational design of caged morpholinos.

    PubMed

    Ouyang, Xiaohu; Shestopalov, Ilya A; Sinha, Surajit; Zheng, Genhua; Pitt, Cameron L W; Li, Wen-Hong; Olson, Andrew J; Chen, James K

    2009-09-23

    Embryogenesis is regulated by genetic programs that are dynamically executed in a stereotypic manner, and deciphering these molecular mechanisms requires the ability to control embryonic gene function with similar spatial and temporal precision. Chemical technologies can enable such genetic manipulations, as exemplified by the use of caged morpholino (cMO) oligonucleotides to inactivate genes in zebrafish and other optically transparent organisms with spatiotemporal control. Here we report optimized methods for the design and synthesis of hairpin cMOs incorporating a dimethoxynitrobenzyl (DMNB)-based bifunctional linker that permits cMO assembly in only three steps from commercially available reagents. Using this simplified procedure, we have systematically prepared cMOs with differing structural configurations and investigated how the in vitro thermodynamic properties of these reagents correlate with their in vivo activities. Through these studies, we have established general principles for cMO design and successfully applied them to several developmental genes. Our optimized synthetic and design methodologies have also enabled us to prepare a next-generation cMO that contains a bromohydroxyquinoline (BHQ)-based linker for two-photon uncaging. Collectively, these advances establish the generality of cMO technologies and will facilitate the application of these chemical probes in vivo for functional genomic studies.

  4. Versatile Synthesis and Rational Design of Caged Morpholinos

    PubMed Central

    2009-01-01

    Embryogenesis is regulated by genetic programs that are dynamically executed in a stereotypic manner, and deciphering these molecular mechanisms requires the ability to control embryonic gene function with similar spatial and temporal precision. Chemical technologies can enable such genetic manipulations, as exemplified by the use of caged morpholino (cMO) oligonucleotides to inactivate genes in zebrafish and other optically transparent organisms with spatiotemporal control. Here we report optimized methods for the design and synthesis of hairpin cMOs incorporating a dimethoxynitrobenzyl (DMNB)-based bifunctional linker that permits cMO assembly in only three steps from commercially available reagents. Using this simplified procedure, we have systematically prepared cMOs with differing structural configurations and investigated how the in vitro thermodynamic properties of these reagents correlate with their in vivo activities. Through these studies, we have established general principles for cMO design and successfully applied them to several developmental genes. Our optimized synthetic and design methodologies have also enabled us to prepare a next-generation cMO that contains a bromohydroxyquinoline (BHQ)-based linker for two-photon uncaging. Collectively, these advances establish the generality of cMO technologies and will facilitate the application of these chemical probes in vivo for functional genomic studies. PMID:19708646

  5. Hydrothermal synthesis of zeolite T from kaolin using two different structure-directing agents

    NASA Astrophysics Data System (ADS)

    Arshad, Sazmal E.; Lutfor Rahman, M.; Sarkar, Shaheen M.; Yusslee, Eddy F.; Patuwan, Siti Z.

    2018-01-01

    Zeolite T was synthesized from the molar chemical composition of 1SiO2:0.04Al2O3:0.26Na2O:0.09K2O:14H2O in the form of a homogenous milky solution in the presence of the two different structure-directing agents TMAOH and TEAOH respectively. Modification of the composition of silica was undertaken using metakaolin from calcined kaolin at 750 °C for 4 h, while the molar composition of each different SDA was variated from 0.05, 0.10, 0.15, 0.20 and 0.25. The homogenous mixture was left at room temperature for 24 h before undergoing hydrothermal synthesis at 100 °C for 168 h. The synthesized samples were filtered and aged at 120 °C for 2 h and each sample was calcined at high temperatures (545 °C for TMAOH and 520 °C for TEAOH) for template removal before characterization using XRD and SEM. Crystallization of the zeolite T in its major form only took place at a molar ratio of 0.10 of TMAOH, while TEAOH showed the species evolution of zeolite T into zeolite L and W for other molar ratios.

  6. Dose-finding designs for trials of molecularly targeted agents and immunotherapies

    PubMed Central

    Chiuzan, Cody; Shtaynberger, Jonathan; Manji, Gulam A.; Duong, Jimmy K.; Schwartz, Gary K.; Ivanova, Anastasia; Lee, Shing M.

    2017-01-01

    Recently, there has been a surge of early phase trials of molecularly targeted agents (MTAs) and immunotherapies. These new therapies have different toxicity profiles compared to cytotoxic therapies. MTAs can benefit from new trial designs that allow inclusion of low-grade toxicities, late-onset toxicities, addition of an efficacy endpoint, and flexibility in the specification of a target toxicity probability. To study the degree of adoption of these methods, we conducted a Web of Science search of articles published between 2008 and 2014 that describe phase 1 oncology trials. Trials were categorized based on the dose-finding design used and the type of drug studied. Out of 1,712 dose-finding trials that met our criteria, 1,591 (92.9%) utilized a rule-based design, and 92 (5.4%; range 2.3% in 2009 to 9.7% in 2014) utilized a model-based or novel design. Over half of the trials tested an MTA or immunotherapy. Among the MTA and immunotherapy trials, 5.8% used model-based methods, compared to 3.9% and 8.3% of the chemotherapy or radiotherapy trials, respectively. While the percentage of trials using novel dose-finding designs has tripled since 2007, only 7.1% of trials use novel designs. PMID:28166468

  7. Synthesis, Aqueous Reactivity, and Biological Evaluation of Carboxylic Acid Ester-Functionalized Platinum–Acridine Hybrid Anticancer Agents

    PubMed Central

    Graham, Leigh A.; Suryadi, Jimmy; West, Tiffany K.; Kucera, Gregory L.; Bierbach, Ulrich

    2012-01-01

    The synthesis of platinum–acridine hybrid agents containing carboxylic acid ester groups is described. The most active derivatives and the unmodified parent compounds showed up to 6-fold higher activity in ovarian cancer (OVCAR-3) and breast cancer (MCF-7, MDA-MB-23) cell lines than cisplatin. Inhibition of cell proliferation at nanomolar concentrations was observed in pancreatic (PANC-1) and non-small cell lung cancer cells (NSCLC, NCI-H460) of 80- and 150-fold, respectively. Introduction of the ester groups did not affect the cytotoxic properties of the hybrids, which form the same monofunctional–intercalative DNA adducts as the parent compounds, as demonstrated in a plasmid unwinding assay. In-line high-performance liquid chromatography and electrospray mass spectrometry (LC-ESMS) shows that the ester moieties undergo platinum-mediated hydrolysis in a chloride concentration-dependent manner to form carboxylate chelates. Potential applications of the chloride-sensitive ester hydrolysis as a self-immolative release mechanism for tumor-selective delivery of platinum–acridines are discussed. PMID:22871158

  8. Little by Little Does the Trick: Design and Construction of a Discrete Event Agent-Based Simulation Framework

    DTIC Science & Technology

    2007-12-01

    model. Finally, we build a small agent-based model using the component architecture to demonstrate the library’s functionality. 15. NUMBER OF...and a Behavioral model. Finally, we build a small agent-based model using the component architecture to demonstrate the library’s functionality...prototypes an architectural design which is generalizable, reusable, and extensible. We have created an initial set of model elements that demonstrate

  9. Aryl sulfonate based anticancer alkylating agents.

    PubMed

    Sheikh, Hamdullah Khadim; Arshad, Tanzila; Kanwal, Ghazala

    2018-05-01

    This research work revolves around synthesis of antineoplastic alkylating sulfonate esters with dual alkylating sites for crosslinking of the DNA strands. These molecules were evaluated as potential antineoplastic cross linking alkylating agents by reaction with the nucleoside of Guanine DNA nucleobase at both ends of the synthesized molecule. Synthesis of the alkylating molecules and the crosslinking with the guanosine nucleoside was monitored by MALDITOF mass spectroscopy. The synthesized molecule's crosslinking or adduct forming rate with the nucleoside was compared with that of 1,4 butane disulfonate (busulfan), in form of time taken for the appearance of [M+H] + . It was found that aryl sulfonate leaving group was causing higher rate of nucleophilic attack by the Lewis basic site of the nucleobase. Furthermore, the rate was also found to be a function of electron withdrawing or donating nature of the substituent on the aryl ring. Compound with strong electron withdrawing substituent on the para position of the ring reacted fastest. Hence, new alkylating agents were synthesized with optimized or desired reactivity.

  10. Design and Synthesis of Novel Block Copolymers for Efficient Opto-Electronic Applications

    NASA Technical Reports Server (NTRS)

    Sun, Sam-Shajing; Fan, Zhen; Wang, Yiqing; Taft, Charles; Haliburton, James; Maaref, Shahin

    2002-01-01

    It has been predicted that nano-phase separated block copolymer systems containing electron rich donor blocks and electron deficient acceptor blocks may facilitate the charge carrier separation and migration in organic photovoltaic devices due to improved morphology in comparison to polymer blend system. This paper presents preliminary data describing the design and synthesis of a novel Donor-Bridge-Acceptor (D-B-A) block copolymer system for potential high efficient organic optoelectronic applications. Specifically, the donor block contains an electron donating alkyloxy derivatized polyphenylenevinylene (PPV), the acceptor block contains an electron withdrawing alkyl-sulfone derivatized polyphenylenevinylene (PPV), and the bridge block contains an electronically neutral non-conjugated aliphatic hydrocarbon chain. The key synthetic strategy includes the synthesis of each individual block first, then couple the blocks together. While the donor block stabilizes and facilitates the transport of the holes, the acceptor block stabilizes and facilitates the transport of the electrons, the bridge block is designed to hinder the probability of electron-hole recombination. Thus, improved charge separation and stability are expected with this system. In addition, charge migration toward electrodes may also be facilitated due to the potential nano-phase separated and highly ordered block copolymer ultra-structure.

  11. 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

  12. Synthesis of aircraft structures using integrated design and analysis methods

    NASA Technical Reports Server (NTRS)

    Sobieszczanski-Sobieski, J.; Goetz, R. C.

    1978-01-01

    A systematic research is reported to develop and validate methods for structural sizing of an airframe designed with the use of composite materials and active controls. This research program includes procedures for computing aeroelastic loads, static and dynamic aeroelasticity, analysis and synthesis of active controls, and optimization techniques. Development of the methods is concerned with the most effective ways of integrating and sequencing the procedures in order to generate structural sizing and the associated active control system, which is optimal with respect to a given merit function constrained by strength and aeroelasticity requirements.

  13. Workflow Agents vs. Expert Systems: Problem Solving Methods in Work Systems Design

    NASA Technical Reports Server (NTRS)

    Clancey, William J.; Sierhuis, Maarten; Seah, Chin

    2009-01-01

    During the 1980s, a community of artificial intelligence researchers became interested in formalizing problem solving methods as part of an effort called "second generation expert systems" (2nd GES). How do the motivations and results of this research relate to building tools for the workplace today? We provide an historical review of how the theory of expertise has developed, a progress report on a tool for designing and implementing model-based automation (Brahms), and a concrete example how we apply 2nd GES concepts today in an agent-based system for space flight operations (OCAMS). Brahms incorporates an ontology for modeling work practices, what people are doing in the course of a day, characterized as "activities." OCAMS was developed using a simulation-to-implementation methodology, in which a prototype tool was embedded in a simulation of future work practices. OCAMS uses model-based methods to interactively plan its actions and keep track of the work to be done. The problem solving methods of practice are interactive, employing reasoning for and through action in the real world. Analogously, it is as if a medical expert system were charged not just with interpreting culture results, but actually interacting with a patient. Our perspective shifts from building a "problem solving" (expert) system to building an actor in the world. The reusable components in work system designs include entire "problem solvers" (e.g., a planning subsystem), interoperability frameworks, and workflow agents that use and revise models dynamically in a network of people and tools. Consequently, the research focus shifts so "problem solving methods" include ways of knowing that models do not fit the world, and ways of interacting with other agents and people to gain or verify information and (ultimately) adapt rules and procedures to resolve problematic situations.

  14. Synthesis route and three different core-shell impacts on magnetic characterization of gadolinium oxide-based nanoparticles as new contrast agents for molecular magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Azizian, Gholamreza; Riyahi-Alam, Nader; Haghgoo, Soheila; Moghimi, Hamid Reza; Zohdiaghdam, Reza; Rafiei, Behrooz; Gorji, Ensieh

    2012-10-01

    Despite its good resolution, magnetic resonance imaging intrinsically has low sensitivity. Recently, contrast agent nanoparticles have been used as sensitivity and contrast enhancer. The aim of this study was to investigate a new controlled synthesis method for gadolinium oxide-based nanoparticle preparation. For this purpose, diethyleneglycol coating of gadolinium oxide (Gd2O3-DEG) was performed using new supervised polyol route, and small particulate gadolinium oxide (SPGO) PEGylation was obtained with methoxy-polyethylene-glycol-silane (550 and 2,000 Da) coatings as SPGO-mPEG-silane550 and 2,000, respectively. Physicochemical characterization and magnetic properties of these three contrast agents in comparison with conventional Gd-DTPA were verified by dynamic light scattering transmission electron microscopy, Fourier transform infrared spectroscopy, inductively coupled plasma, X-ray diffraction, vibrating sample magnetometer, and the signal intensity and relaxivity measurements were performed using 1.5-T MRI scanner. As a result, the nanoparticle sizes of Gd2O3-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000 could be reached to 5.9, 51.3, 194.2 nm, respectively. The image signal intensity and longitudinal ( r 1) and transverse relaxivity ( r 2) measurements in different concentrations (0.3 to approximately 2.5 mM), revealed the r 2/ r 1 ratios of 1.13, 0.89, 33.34, and 33.72 for Gd-DTPA, Gd2O3-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000, respectively. The achievement of new synthesis route of Gd2O3-DEG resulted in lower r 2/ r 1 ratio for Gd2O3-DEG than Gd-DTPA and other previous synthesized methods by this and other groups. The smaller r 2/ r 1 ratios of two PEGylated-SPGO contrast agents in our study in comparison with r 2/ r 1 ratio of previous PEGylation ( r 2/ r 1 = 81.9 for mPEG-silane 6,000 MW) showed that these new three introduced contrast agents could potentially be proper contrast enhancers for cellular and molecular MR imaging.

  15. Synthesis of Enantiomerically Pure Anthracyclinones

    NASA Astrophysics Data System (ADS)

    Achmatowicz, Osman; Szechner, Barbara

    The anthracycline antibiotics are among the most important clinical drugs used in the treatment of human cancer. The search for new agents with improved therapeutic efficacy and reduced cardiotoxicity stimulated considerable efforts in the synthesis of new analogues. Since the biological activity of anthracyclines depends on their natural absolute configuration, various strategies for the synthesis of enantiomerically pure anthracyclinones (aglycones) have been developed. They comprise: resolution of racemic intermediate, incorporation of a chiral fragment derived from natural and non-natural chiral pools, asymmetric synthesis with the use of a chiral auxiliary or a chiral reagent, and enantioselective catalysis. Synthetic advances towards enantiopure anthracyclinones reported over the last 17 years are reviewed.

  16. Development of weight/sizing design synthesis computer program. Volume 3: User Manual

    NASA Technical Reports Server (NTRS)

    Garrison, J. M.

    1973-01-01

    The user manual for the weight/sizing design synthesis program is presented. The program is applied to an analysis of the basic weight relationships for the space shuttle which contribute significant portions of the inert weight. The relationships measure the parameters of load, geometry, material, and environment. A verbal description of the processes simulated, data input procedures, output data, and values present in the program is included.

  17. A chemical reduction approach to the synthesis of copper nanoparticles

    NASA Astrophysics Data System (ADS)

    Khan, Ayesha; Rashid, Audil; Younas, Rafia; Chong, Ren

    2016-11-01

    Development of improved methods for the synthesis of copper nanoparticles is of high priority for the advancement of material science and technology. Herein, starch-protected zero-valent copper (Cu) nanoparticles have been successfully synthesized by a novel facile route. The method is based on the chemical reduction in aqueous copper salt using ascorbic acid as reducing agent at low temperature (80 °C). X-ray diffraction, scanning electron microscopy and energy-dispersive X-ray spectroscopy measurements were taken to investigate the size, structure and composition of synthesized Cu nanocrystals, respectively. Average crystallite size of Cu nanocrystals calculated from the major diffraction peaks using the Scherrer formula is about 28.73 nm. It is expected that the outcomes of the study take us a step closer toward designing rational strategies for the synthesis of nascent Cu nanoparticles without inert gas protection.

  18. 4-haloethenylphenyl tropane:serotonin transporter imaging agents

    DOEpatents

    Goodman, Mark M.; Martarello, Laurent

    2005-01-18

    A series of compounds in the 4-fluoroalkyl-3-halophenyl nortropanes and 4-haloethenylphenyl tropane families are described as diagnostic and therapeutic agents for diseases associated with serotonin transporter dysfunction. These compounds bind to serotonin transporter protein with high affinity and selectivity. The invention provides methods of synthesis which incorporate radioisotopic halogens at a last step which permit high radiochemical yield and maximum usable product life. The radiolabeled compounds of the invention are useful as imaging agents for visualizing the location and density of serotonin transporter by PET and SPECT imaging.

  19. N-methyldiethanolamine: a multifunctional structure-directing agent for the synthesis of SAPO and AlPO molecular sieves.

    PubMed

    Wang, Dehua; Tian, Peng; Fan, Dong; Yang, Miao; Gao, Beibei; Qiao, Yuyan; Wang, Chan; Liu, Zhongmin

    2015-05-01

    In the present study, N-methyldiethanolamine (MDEA) is demonstrated to be a multifunctional structure-directing agent for the synthesis of aluminophosphate-based molecular sieves. Four types of molecular sieves, including SAPO-34, -35, AlPO-9 and -22, are for the first time acquired with MDEA as a novel template. The phase selectivity of the present synthesis is found to be condition-dependent. SAPO-34 (CHA) crystallizes from a conventional hydrothermal system with a higher MDEA concentration. When using MDEA as both the template and solvent, pure SAPO-35 (LEV) is obtained from the synthetic gel with a high P2O5/Al2O3 ratio of (2-3), in which the concentration of MDEA could be varied in a wide range. AlPO-9 and AlPO-22 (AWW) are synthesized under the similar conditions to SAPO-35, except without the addition of Si source. The physicochemical properties of the obtained samples are investigated by XRD, XRF, SEM, N2 physisorption, TG-DSC, and various NMR spectra ((13)C, (29)Si, (27)Al and (31)P). Both SAPO-34 and SAPO-35 show good thermal stability, large surface area, and high pore volume. The catalytic performance of SAPO-34 is evaluated by the methanol-to-olefins (MTO) reaction and a good (C2H4+C3H6) selectivity of 82.7% has been achieved. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Cellulose as an adhesion agent for the synthesis of lignin aerogel with strong mechanical performance, Sound-absorption and thermal Insulation

    PubMed Central

    Wang, Chao; Xiong, Ye; Fan, Bitao; Yao, Qiufang; Wang, Hanwei; Jin, Chunde; Sun, Qingfeng

    2016-01-01

    The lignin aerogels that are both high porosity and compressibility would have promising implications for bioengineering field to sound-adsorption and damping materials; however, creating this aerogel had a challenge to adhesive lignin. Here we reported cellulose as green adhesion agent to synthesize the aerogels with strong mechanical performance. Our approach—straightforwardly dissolved in ionic liquids and simply regenerated in the deionized water—causes assembly of micro-and nanoscale and even molecule level of cellulose and lignin. The resulting lignin aerogels exhibit Young’s modulus up to 25.1 MPa, high-efficiency sound-adsorption and excellent thermal insulativity. The successful synthesis of this aerogels developed a path for lignin to an advanced utilization. PMID:27562532

  1. Pervasive surveillance-agent system based on wireless sensor networks: design and deployment

    NASA Astrophysics Data System (ADS)

    Martínez, José F.; Bravo, Sury; García, Ana B.; Corredor, Iván; Familiar, Miguel S.; López, Lourdes; Hernández, Vicente; Da Silva, Antonio

    2010-12-01

    Nowadays, proliferation of embedded systems is enhancing the possibilities of gathering information by using wireless sensor networks (WSNs). Flexibility and ease of installation make these kinds of pervasive networks suitable for security and surveillance environments. Moreover, the risk for humans to be exposed to these functions is minimized when using these networks. In this paper, a virtual perimeter surveillance agent, which has been designed to detect any person crossing an invisible barrier around a marked perimeter and send an alarm notification to the security staff, is presented. This agent works in a state of 'low power consumption' until there is a crossing on the perimeter. In our approach, the 'intelligence' of the agent has been distributed by using mobile nodes in order to discern the cause of the event of presence. This feature contributes to saving both processing resources and power consumption since the required code that detects presence is the only system installed. The research work described in this paper illustrates our experience in the development of a surveillance system using WNSs for a practical application as well as its evaluation in real-world deployments. This mechanism plays an important role in providing confidence in ensuring safety to our environment.

  2. CDK1 promotes nascent DNA synthesis and induces resistance of cancer cells to DNA-damaging therapeutic agents

    PubMed Central

    Liao, Hongwei; Ji, Fang; Geng, Xinwei; Xing, Meichun; Li, Wen; Chen, Zhihua; Shen, Huahao; Ying, Songmin

    2017-01-01

    Cyclin dependent kinase 1 (CDK1) is essential for cell viability and plays a vital role in many biological events including cell cycle control, DNA damage repair, and checkpoint activation. Here, we identify an unanticipated role for CDK1 in promoting nascent DNA synthesis during S-phase. We report that a short duration of CDK1 inhibition, which does not perturb cell cycle progression, triggers a replication-associated DNA damage response (DDR). This DDR is associated with a disruption of replication fork progression and leads to genome instability. Moreover, we show that compromised CDK1 activity dramatically increases the efficacy of chemotherapeutic agents that kill cancer cells through perturbing DNA replication, including Olaparib, an FDA approved PARP inhibitor. Our study has revealed an important role for CDK1 in the DNA replication program, and suggests that the therapeutic targeting CDK1 may be a novel approach for combination chemotherapy. PMID:29207595

  3. Design and synthesis of diverse functional kinked nanowire structures for nanoelectronic bioprobes.

    PubMed

    Xu, Lin; Jiang, Zhe; Qing, Quan; Mai, Liqiang; Zhang, Qingjie; Lieber, Charles M

    2013-02-13

    Functional kinked nanowires (KNWs) represent a new class of nanowire building blocks, in which functional devices, for example, nanoscale field-effect transistors (nanoFETs), are encoded in geometrically controlled nanowire superstructures during synthesis. The bottom-up control of both structure and function of KNWs enables construction of spatially isolated point-like nanoelectronic probes that are especially useful for monitoring biological systems where finely tuned feature size and structure are highly desired. Here we present three new types of functional KNWs including (1) the zero-degree KNW structures with two parallel heavily doped arms of U-shaped structures with a nanoFET at the tip of the "U", (2) series multiplexed functional KNW integrating multi-nanoFETs along the arm and at the tips of V-shaped structures, and (3) parallel multiplexed KNWs integrating nanoFETs at the two tips of W-shaped structures. First, U-shaped KNWs were synthesized with separations as small as 650 nm between the parallel arms and used to fabricate three-dimensional nanoFET probes at least 3 times smaller than previous V-shaped designs. In addition, multiple nanoFETs were encoded during synthesis in one of the arms/tip of V-shaped and distinct arms/tips of W-shaped KNWs. These new multiplexed KNW structures were structurally verified by optical and electron microscopy of dopant-selective etched samples and electrically characterized using scanning gate microscopy and transport measurements. The facile design and bottom-up synthesis of these diverse functional KNWs provides a growing toolbox of building blocks for fabricating highly compact and multiplexed three-dimensional nanoprobes for applications in life sciences, including intracellular and deep tissue/cell recordings.

  4. Synthesis and characterization of polyethylenimine-based iron oxide composites as novel contrast agents for MRI.

    PubMed

    Masotti, A; Pitta, A; Ortaggi, G; Corti, M; Innocenti, C; Lascialfari, A; Marinone, M; Marzola, P; Daducci, A; Sbarbati, A; Micotti, E; Orsini, F; Poletti, G; Sangregorio, C

    2009-04-01

    Use of polyethylenimines (PEIs) of different molecular weight and selected carboxylated-PEI derivatives (PEI-COOH) in the synthesis and stabilization of iron oxide nanoparticles, to obtain possible multifunctional contrast agents. Oxidation of Fe(II) at slightly elevated pH and temperature resulted in the formation of highly soluble and stable nanocomposites of iron oxides and polymer. Composites were characterized and studied by atomic force microscopy (AFM), transmission electron microscopy (TEM), X-ray diffractometry, AC and DC magnetometry, NMR relaxometry and magnetic resonance imaging (MRI). From AFM the dimensions of the aggregates were found to be in the ~150-250 nm size region; the mean diameter of the magnetic core of the compounds named PEI-25, PEI-500 and PEI-COOH60 resulted d approximately 20 +/- 5 nm for PEI-25, d approximately 9.5 +/- 1.0 nm for PEI-500 and d approximately 6.8 +/- 1.0 nm for PEI-COOH60. In PEI-COOH60 TEM and X-ray diffractometry revealed small assemblies of mineral magnetic cores with clear indications that the main constituents are maghemite and/or magnetite as confirmed by AC and DC SQUID magnetometry. For PEI-COOH60, the study of NMR-dispersion profiles revealed r (1) and r (2) relaxivities comparable to superparamagnetic iron-oxide commercial compounds in the whole investigated frequency range 7 < or = nu < or = 212 MHz. PEI-25 was studied as possible MRI contrast agent (CA) to map the cerebral blood volume (CBV) and cerebral blood flow (CBF) in an animal model obtaining promising results. The reported compounds may be further functionalized to afford novel multifunctional systems for biomedical applications.

  5. The INVEST project: investigating the use of evidence synthesis in the design and analysis of clinical trials.

    PubMed

    Clayton, Gemma L; Smith, Isabelle L; Higgins, Julian P T; Mihaylova, Borislava; Thorpe, Benjamin; Cicero, Robert; Lokuge, Kusal; Forman, Julia R; Tierney, Jayne F; White, Ian R; Sharples, Linda D; Jones, Hayley E

    2017-05-15

    When designing and analysing clinical trials, using previous relevant information, perhaps in the form of evidence syntheses, can reduce research waste. We conducted the INVEST (INVestigating the use of Evidence Synthesis in the design and analysis of clinical Trials) survey to summarise the current use of evidence synthesis in trial design and analysis, to capture opinions of trialists and methodologists on such use, and to understand any barriers. Our sampling frame was all delegates attending the International Clinical Trials Methodology Conference in November 2015. Respondents were asked to indicate (1) their views on the use of evidence synthesis in trial design and analysis, (2) their own use during the past 10 years and (3) the three greatest barriers to use in practice. Of approximately 638 attendees of the conference, 106 (17%) completed the survey, half of whom were statisticians. Support was generally high for using a description of previous evidence, a systematic review or a meta-analysis in trial design. Generally, respondents did not seem to be using evidence syntheses as often as they felt they should. For example, only 50% (42/84 relevant respondents) had used a meta-analysis to inform whether a trial is needed compared with 74% (62/84) indicating that this is desirable. Only 6% (5/81 relevant respondents) had used a value of information analysis to inform sample size calculations versus 22% (18/81) indicating support for this. Surprisingly large numbers of participants indicated support for, and previous use of, evidence syntheses in trial analysis. For example, 79% (79/100) of respondents indicated that external information about the treatment effect should be used to inform aspects of the analysis. The greatest perceived barrier to using evidence synthesis methods in trial design or analysis was time constraints, followed by a belief that the new trial was the first in the area. Evidence syntheses can be resource-intensive, but their use in

  6. Facile synthesis and application of a carbon foam with large mesopores.

    PubMed

    Fu, Liling; Qi, Genggeng; Sahore, Ritu; Sougrat, Rachid; DiSalvo, Francis J; Giannelis, Emmanuel P

    2013-11-28

    By combining elements of hard- and soft-templating, a facile synthesis method for carbon foams with large mesopores has been demonstrated. A commercial Pluronic surfactant was used as the structure-directing agent as well as the carbon precursor. No micelle swelling agent or post treatment is necessary to enlarge mesopores. As such this method requires fewer synthesis steps and is highly scalable. The as-synthesized meso-carbons showed potential applications in the fields of carbon oxide capture and lithium-sulfur batteries.

  7. Synthesis of novel (2R,4R)- and (2S,4S)-iso dideoxynucleosides with exocyclic methylene as potential antiviral agents.

    PubMed

    Yoo, Su Jeong; Kim, Hea Ok; Lim, Yoongho; Kim, Jeongmin; Jeong, Lak Shin

    2002-01-01

    Novel (2R,4R)- and (2S,4S)-iso dideoxynucleosides with exocyclic methylene have been designed and synthesized, based on the lead BMS-200475 (3) which exhibited potent anti-HBV activity. For the synthesis of D types of (2R,4R)-nucleosides, L-xylose was converted to the key intermediate 14. The intermediate 14 was converted to the uracil derivative 4a and the cytosine derivative 4b. Compound 14 was also converted to the purine derivatives such as adenine derivative 4c, hypoxanthine derivative 4d, and guanine derivative 4e. The corresponding L types of (2S,4S)-enantiomers were more efficiently synthesized from the commercially available 1,2-isopropylidene-D-xylose (20) than the synthetic method used in the synthesis of (2R,4R)-nucleosides. The key intermediate 25 was converted to the pyrimidine analogues 5a and 5b and the purine derivatives 5c, 5d, and 5e using the similar method used in the preparation of 4c, 4d, and 4e. The synthesized final (2R,4R)- and (2S,4S)-nucleosides were tested against several viruses such as HIV-1, HSV-1, HSV-2, HCMV and HBV. (2R,4R)-Adenine analogue 4c exhibited potent anti-HBV activity (EC(50)=1.5 microM in 2.2.15 cells) among compounds tested, while (2R,4R)-uracil derivative 4a was the most active against HCMV among compounds tested and (2R,4R)-adenine derivative 4c was found to be moderately active against the same virus. However, the corresponding (2S,4S)-isomers were found to be totally inactive against all tested viruses. Both (2R,4R)-adenine derivative 4c and (2S,4S)-adenine analogue 5c were totally resistant to the adenosine deaminase like iso-ddA (1). From the molecular modeling study the hydroxymethyl side chains of BMS-200475 (3) and 4c were almost overlapped, indicating that 4c may be suitable for phosphorylation by cellular kinases like the lead 3, but some discrepancy between two bases was observed, indicating why 4c is less potent against HBV than 3. It is concluded that discovery of (2R,4R)-adenine analogue 4c as potent

  8. DNA excision repair in cell extracts from human cell lines exhibiting hypersensitivity to DNA-damaging agents

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

    Hansson, J.; Keyse, S.M.; Lindahl, T.

    Whole cell extracts from human lymphoid cell lines can perform in vitro DNA repair synthesis in plasmids damaged by agents including UV or cis-diamminedichloroplatinum(II) (cis-DDP). Extracts from xeroderma pigmentosum (XP) cells are defective in repair synthesis. We have now studied in vitro DNA repair synthesis using extracts from lymphoblastoid cell lines representing four human hereditary syndromes with increased sensitivity to DNA-damaging agents. Extracts of cell lines from individuals with the sunlight-sensitive disorders dysplastic nevus syndrome or Cockayne's syndrome (complementation groups A and B) showed normal DNA repair synthesis in plasmids with UV photoproducts. This is consistent with in vivo measurementsmore » of the overall DNA repair capacity in such cell lines. A number of extracts were prepared from two cell lines representing the variant form of XP (XP-V). Half of the extracts prepared showed normal levels of in vitro DNA repair synthesis in plasmids containing UV lesions, but the remainder of the extracts from the same cell lines showed deficient repair synthesis, suggesting the possibility of an unusually labile excision repair protein in XP-V. Fanconi's anemia (FA) cells show cellular hypersensitivity to cross-linking agents including cis-DDP. Extracts from cell lines belonging to two different complementation groups of FA showed normal DNA repair synthesis in plasmids containing cis-DDP or UV adducts. Thus, there does not appear to be an overall excision repair defect in FA, but the data do not exclude a defect in the repair of interstrand DNA cross-links.« less

  9. Proceedings of the Agent 2002 Conference on Social Agents : Ecology, Exchange, and Evolution

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

    Macal, C., ed.; Sallach, D., ed.

    2003-04-10

    Welcome to the ''Proceedings'' of the third in a series of agent simulation conferences cosponsored by Argonne National Laboratory and The University of Chicago. The theme of this year's conference, ''Social Agents: Ecology, Exchange and Evolution'', was selected to foster the exchange of ideas on some of the most important social processes addressed by agent simulation models, namely: (1) The translation of ecology and ecological constraints into social dynamics; (2) The role of exchange processes, including the peer dependencies they create; and (3) The dynamics by which, and the attractor states toward which, social processes evolve. As stated in themore » ''Call for Papers'', throughout the social sciences, the simulation of social agents has emerged as an innovative and powerful research methodology. The promise of this approach, however, is accompanied by many challenges. First, modeling complexity in agents, environments, and interactions is non-trivial, and these representations must be explored and assessed systematically. Second, strategies used to represent complexities are differentially applicable to any particular problem space. Finally, to achieve sufficient generality, the design and experimentation inherent in agent simulation must be coupled with social and behavioral theory. Agent 2002 provides a forum for reviewing the current state of agent simulation scholarship, including research designed to address such outstanding issues. This year's conference introduces an extensive range of domains, models, and issues--from pre-literacy to future projections, from ecology to oligopolistic markets, and from design to validation. Four invited speakers highlighted major themes emerging from social agent simulation.« less

  10. Synthesis and evaluation of novel Tc-99m labeled NGR-containing hexapeptides as tumor imaging agents.

    PubMed

    Kim, Dae-Weung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Kim, Chang Guhn

    2015-02-01

    Asparagine-glycine-arginine (NGR)-containing peptides targeting aminopeptidase N (APN)/CD13 can be an excellent candidate for targeting ligands in molecular tumor imaging. In this study, we developed two NGR-containing hexapeptides, and evaluated the diagnostic performance of Tc-99m labeled hexapeptides as molecular imaging agents in an HT-1080 fibrosarcoma-bearing murine model. Peptides were synthesized using Fmoc solid-phase peptide synthesis. Radiochemical purity of Tc-99m was evaluated using instant thin-layer chromatography. The uptake of two NGR-containing hexapeptides within HT-1080 cells was evaluated in vitro. In HT-1080 fibrosarcoma tumor-bearing mice, gamma images were acquired. A biodistribution study was performed to calculate percentage of the injected dose per gram of tissue (%ID/g). Two hexapeptides, glutamic acid-cysteine-glycine (ECG)-NGR and NGR-ECG were successfully synthesized. After radiolabeling procedures with Tc-99m, the complexes Tc-99m hexapeptides were prepared in high yield. The uptake of Tc-99m ECG-NGR within the tumor cells had been assured by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-NGR was accumulated substantially in the subcutaneously engrafted tumor. However, Tc-99m NGR-ECG was accumulated minimally in the tumor. Two NGR-containing hexapeptides, ECG-NGR and NGR-ECG were developed as molecular imaging agents to target APN/CD13 in HT-1080 fibrosarcoma. Tc-99m ECG-NGR showed a significant uptake in the tumor, and it is a good candidate for tumor imaging. Copyright © 2015 John Wiley & Sons, Ltd.

  11. TACtic- A Multi Behavioral Agent for Trading Agent Competition

    NASA Astrophysics Data System (ADS)

    Khosravi, Hassan; Shiri, Mohammad E.; Khosravi, Hamid; Iranmanesh, Ehsan; Davoodi, Alireza

    Software agents are increasingly being used to represent humans in online auctions. Such agents have the advantages of being able to systematically monitor a wide variety of auctions and then make rapid decisions about what bids to place in what auctions. They can do this continuously and repetitively without losing concentration. To provide a means of evaluating and comparing (benchmarking) research methods in this area the trading agent competition (TAC) was established. This paper describes the design, of TACtic. Our agent uses multi behavioral techniques at the heart of its decision making to make bidding decisions in the face of uncertainty, to make predictions about the likely outcomes of auctions, and to alter the agent's bidding strategy in response to the prevailing market conditions.

  12. Design and synthesis of 2-nitroimidazoles with variable alkylating and acylating functionality.

    PubMed

    Winters, Thomas; Sercel, Anthony; Suto, Carla; Elliott, William; Leopold, Wilbur; Leopold, Judith; Showalter, Hollis

    2014-01-01

    The synthesis of a small series of 2-nitroimidazoles in which the β-amino alcohol side chain was amidated with a range of alkylating/acylating functionality is described. Synthetic methodologies were developed that generally provided for selective N-acyl versus N,O-bisacyl products. In vitro, target analogs showed minimal radiosensitization activity, with only a few exhibiting a sensitizer enhancement ratio (SER) >2.0 and C(1.6) values comparable to reference agents RB-6145 and RSU-1069. In an assay to determine potential to alkylate biomolecules, representative analogs showed <1% of the alkylating activity of RSU-1069. In vivo, one analog showed an enhancement ratio of 1.6 relative to vehicle control when tested in B6C3F1 mice with an implanted KHT sarcoma. The data reinforce prior findings that there is a correlation between alkylation potential and in vivo activity.

  13. Hybrid calcium carbonate/polymer microparticles containing silver nanoparticles as antibacterial agents

    NASA Astrophysics Data System (ADS)

    Długosz, Maciej; Bulwan, Maria; Kania, Gabriela; Nowakowska, Maria; Zapotoczny, Szczepan

    2012-12-01

    We report here on synthesis and characterization of novel hybrid material consisting of silver nanoparticles (nAgs) embedded in calcium carbonate microparticles (μ-CaCO3) serving as carriers for sustained release. nAgs are commonly used as antimicrobial agents in many commercial products (textiles, cosmetics, and drugs). Although they are considered to be safe, their interactions with human organisms are still not fully understood; therefore it is important to apply them with caution and limit their presence in the environment. The synthesis of the new material was based on the co-precipitation of CaCO3 and nAg in the presence of poly(sodium 4-styrenesulfonate). Such designed system enables sustained release of nAg to the environment. This hybrid colloidal material (nAg/μ-CaCO3) was characterized by microscopic and spectroscopic methods. The release of nAg from μ-CaCO3 microparticles was followed in water at various pH values. Microbiological tests confirmed the effectiveness of these microparticles as an antibacterial agent. Importantly, the material can be stored as a dry powder and subsequently re-suspended in water without the risk of losing its antimicrobial activity. nAg/μ-CaCO3 was applied here to insure bacteriostatic properties of down feathers that may significantly prolong their lifetime in typical applications. Such microparticles may be also used as, e.g., components of coatings and paints protecting various surfaces against microorganism colonization.

  14. Reducing agent-free synthesis of curcumin-loaded albumin nanoparticles by self-assembly at room temperature.

    PubMed

    Safavi, Maryam Sadat; Shojaosadati, Seyed Abbas; Yang, Hye Gyeong; Kim, Yejin; Park, Eun Ji; Lee, Kang Choon; Na, Dong Hee

    2017-08-30

    The purpose of this study was to prepare curcumin-loaded bovine serum albumin nanoparticles (CCM-BSA-NPs) by reducing agent-free self-assembly at room temperature. A 2 4 factorial design approach was used to investigate the CCM-BSA-NP preparation process at different pH values, temperatures, dithiothreitol amounts, and CCM/BSA mass ratios. Increasing the ionic strength enabled preparation of CCM-BSA-NPs at 25°C without reducing agent. CCM-BSA-NPs prepared under the optimized conditions at 25°C showed a particle size of 110±6nm, yield of 88.5%, and drug loading of 7.1%. The CCM-BSA-NPs showed strong antioxidant activity and neuroprotective effects in glutamate-induced mouse hippocampal neuronal HT22 cells. This study suggests that ionic strength can be a key parameter affecting the preparation of albumin-based NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer

    DTIC Science & Technology

    2015-12-01

    normal DNA synthesis. In contrast, pol eta shows a combination of high efficiency and low fidelity when replicating 8-oxo-G. These combined properties...are consistent with a pro- mutagenic role for pol eta when replicating this DNA lesion under cellular conditions. Studies with modified nucleotide...analogs indicate that pol eta relies heavily on hydrogen-bonding interactions during normal and translesion synthesis. However, some nucleobase

  16. Carbohydrate-directed synthesis of silver and gold nanoparticles: effect of the structure of carbohydrates and reducing agents on the size and morphology of the composites.

    PubMed

    Shervani, Zameer; Yamamoto, Yasushi

    2011-04-01

    A monosaccharide (β-D-glucose) and polysaccharide (soluble starch) were used as structure directing and subsequently stabilizing agents for the synthesis of spherical nanoparticles (NPs) and nanowires of silver and gold. Homogeneous monodispersed Ag(0) nanoparticles (Ag NPs) of 15 nm diameter were obtained when 10(-4)M AgNO(3) precursor salt was reduced in starch (1 wt%)-water gel by 1 wt% β-D-glucose. For a second preparation the effect of reducing agents on the synthesis of Au(0) metallic nanoparticles (Au NPs) of 2 × 10(-4)M concentration prepared in a β-D-glucose (0.03 M)-water dispersion was studied first in detail. Different equivalent amounts of NaBH(4) and a number of pH values were evaluated for the reduction of the Au salt HAuCl(4)·3H(2)O to obtain Au NPs. The type and the amount of reducing agent, as well as the pH of the solution was shown to affect the size and morphology of the NPs. NaBH(4) (4 equiv) produced the smallest (5.3 nm (σ 0.7)) metallic particles compared to larger particles (10.0 nm (σ 1.4)) when the salt was reduced by 1 equiv of NaBH(4). Addition of excess NaBH(4) caused the NPs to settle out as a precipitate forming a mesh or wire structure rather than monodispersed particles. Low pH (pH 6) resulted in incomplete reduction, while at pH 8 the salt was completely reduced. When the salt was reduced by NaOH at pH 8, the particles were larger (14.2 nm) and less homogeneous (σ 2.8) compared to those from NaBH(4) reduction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Nanocarriers for delivery of siRNA and co-delivery of siRNA and other therapeutic agents.

    PubMed

    Zhao, Jing; Feng, Si-Shen

    2015-07-01

    A major problem in cancer treatment is the multidrug resistance. siRNA inhibitors have great advantages to solve the problem, if the bottleneck of their delivery could be well addressed by the various nanocarriers. Moreover, co-delivery of siRNA together with the various anticancer agents in one nanocarrier may maximize their additive or synergistic effect. This review provides a comprehensive summary on the state-of-the-art of the nanocarriers, which may include prodrugs, micelles, liposomes, dendrimers, nanohydrogels, solid lipid nanoparticles, nanoparticles of biodegradable polymers and nucleic acid nanocarriers for delivery of siRNA and co-delivery of siRNA together with anticancer agents with focus on synthesis of the nanocarrier materials, design and characterization, in vitro and in vivo evaluation, and prospect and challenges of nanocarriers.

  18. Heterocyclic energetic materials: Synthesis, characterization and computational design

    NASA Astrophysics Data System (ADS)

    Tsyshevsky, Roman; Pagoria, Philip; Smirnov, Aleksander; Kuklja, Maija

    2017-06-01

    Achievement of the tailored properties (high performance, low sensitivity, etc.) in targeted new energetic materials (EM) remains a great challenge. Recently, attention of researchers has shifted from conventional nitroester-, nitramine-, and nitroaromatic-based explosives to new heterocyclic EM with oxygen- and nitrogenrich molecular structures. They have increased densities and formation enthalpies complemented by attractive performance and high stability to external stimuli. We will demonstrate that oxadiazol-containing heterocycles offer a convenient playground to probe specific chemical functional groups as building blocks for design of EM. We discuss a joint experimental and computational approach for design, characterization, synthesis, and modeling of novel heterocyclic EM. Combinatorically, we comprehensively analyzed how overall stability and performance of each material in the family (BNFF, LLM-172, LLM-175, LLM-191, LLM-192, LLM-200) depends upon their chemical composition and details of the molecular structure (such as a substitution of a nitro group by an amino group and 1,2,5-oxadiazole fragment by 1,2,3- or 1,2,4-oxadiazol ring). We will also discuss proposed new EM with predicted superior chemical and physical properties. P. Pagoria, R. Tsyshevsky, A. Smirnov.

  19. Bioactive Glass Nanoparticles: From Synthesis to Materials Design for Biomedical Applications

    PubMed Central

    Vichery, Charlotte; Nedelec, Jean-Marie

    2016-01-01

    Thanks to their high biocompatibility and bioactivity, bioactive glasses are very promising materials for soft and hard tissue repair and engineering. Because bioactivity and specific surface area intrinsically linked, the last decade has seen a focus on the development of highly porous and/or nano-sized materials. This review emphasizes the synthesis of bioactive glass nanoparticles and materials design strategies. The first part comprehensively covers mainly soft chemistry processes, which aim to obtain dispersible and monodispersed nanoparticles. The second part discusses the use of bioactive glass nanoparticles for medical applications, highlighting the design of materials. Mesoporous nanoparticles for drug delivery, injectable systems and scaffolds consisting of bioactive glass nanoparticles dispersed in a polymer, implant coatings and particle dispersions will be presented. PMID:28773412

  20. Synthesis of Fucosylated Chondroitin Sulfate Glycoclusters: A Robust Route to New Anticoagulant Agents.

    PubMed

    Zhang, Xiao; Yao, Wang; Xu, Xiaojiang; Sun, Huifang; Zhao, Jinhua; Meng, Xiangbao; Wu, Mingyi; Li, Zhongjun

    2018-02-01

    Fucosylated chondroitin sulfate (FuCS) is a structurally distinct glycosaminoglycan with excellent anticoagulant activity. Studies show that FuCS and its depolymerized fragments exhibit a different anticoagulant mechanism from that of heparin derivatives, with decreased risks of adverse effects and bleeding. However, further exploitation has been hindered by the scarcity of structurally defined oligosaccharides. Herein, facile method is reported for the synthesis of the repeating trisaccharide unit of FuCS based on the degradation of chondroitin sulfate polymers. A series of simplified FuCS glycomimetics that have highly tunable structures, controllable branches, and defined sulfation motifs were generated by copper-catalyzed alkyne-azide cycloaddition. Remarkable improvement in activated partial thromboplastin time (APTT) assay activities was observed as the branches increased, but no significant influences were observed for prothrombin time (PT) and thrombin time (TT) assay activities. Further FXase inhibition tests suggested that glycoclusters 33 b-40 b selectively inhibited intrinsic anticoagulant activities, but had little effect on the extrinsic and common coagulation pathways. Notably, glycoclusters with the 2,4-di-O-sulfated fucosyl residue displayed the most potency, which was in consistent with that of natural polysaccharides. These FuCS clusters demonstrated potency to mimic linear glycosaminoglycans and offer a new framework for the development of novel anticoagulant agents. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Multi-Agent Systems Design for Novices

    ERIC Educational Resources Information Center

    Lynch, Simon; Rajendran, Keerthi

    2005-01-01

    Advanced approaches to the construction of software systems can present difficulties to learners. This is true for multi-agent systems (MAS) which exhibit concurrency, non-determinacy of structure and composition and sometimes emergent behavior characteristics. Additional barriers exist for learners because mainstream MAS technology is young and…

  2. Green synthesis of gold nanoparticles using aqueous ethanol extract of Curcuma mangga rhizomes as reducing agent

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

    Yee, Foo Yiing; Malek, Sri Nurestri Abd; Periasamy, Vengadesh

    Green synthesis of gold nanoparticles (AuNPs) had been developed as an alternative to chemical and physical methods due to its simplicity, cost effectiveness and eco-friendliness. The high biocompatibility and biostability features of AuNPs have found importance in biomedical applications in recent years. In this study, aqueous ethanol extract of Curcuma mangga rhizomes which acts as reducing and stabilizing agent was used to synthesize stable AuNPs by bioreduction of chloroauric acid. The formation of AuNPs was highlighted by the color change of the suspension from light yellow to reddish purple. Time-evolution was monitored by UV-visible spectroscopy, while surface plasmon (SP) absorptionmore » band of the AuNPs suspension was observed at a maximum absorption of 540 nm. Hydrodynamic radii and size distribution of the AuNPs in the suspension were evaluated using dynamic light scattering (DLS) and zeta potential measurement demonstrated negative surface charge. The particle size was calculated in the range of 2-30 nm using High Resolution Transmission Electron Microscopy (HRTEM). The morphology and elemental composition were further determined by Field Effect Scanning Electron Microscopy (FESEM) and Energy Dispersive X-ray (EDX) spectroscopy. Fourier transform infrared (FTIR) spectroscopy meanwhile was used to confirm the presence of AuNPs and functional groups involved in the gold bio-reduction process. Influence of the volume of extract and concentration of gold (III) chloride trihydrate (HAuCl{sub 4}.3H{sub 2}O) on the synthesis of AuNPs were also investigated. The results obtained indicate potential optimization and functionalization of AuNPs for future applications in bionanotechnology especially in the field of medicine.« less

  3. Green synthesis of gold nanoparticles using aqueous ethanol extract of Curcuma mangga rhizomes as reducing agent

    NASA Astrophysics Data System (ADS)

    Yee, Foo Yiing; Periasamy, Vengadesh; Malek, Sri Nurestri Abd

    2015-04-01

    Green synthesis of gold nanoparticles (AuNPs) had been developed as an alternative to chemical and physical methods due to its simplicity, cost effectiveness and eco-friendliness. The high biocompatibility and biostability features of AuNPs have found importance in biomedical applications in recent years. In this study, aqueous ethanol extract of Curcuma mangga rhizomes which acts as reducing and stabilizing agent was used to synthesize stable AuNPs by bioreduction of chloroauric acid. The formation of AuNPs was highlighted by the color change of the suspension from light yellow to reddish purple. Time-evolution was monitored by UV-visible spectroscopy, while surface plasmon (SP) absorption band of the AuNPs suspension was observed at a maximum absorption of 540 nm. Hydrodynamic radii and size distribution of the AuNPs in the suspension were evaluated using dynamic light scattering (DLS) and zeta potential measurement demonstrated negative surface charge. The particle size was calculated in the range of 2-30 nm using High Resolution Transmission Electron Microscopy (HRTEM). The morphology and elemental composition were further determined by Field Effect Scanning Electron Microscopy (FESEM) and Energy Dispersive X-ray (EDX) spectroscopy. Fourier transform infrared (FTIR) spectroscopy meanwhile was used to confirm the presence of AuNPs and functional groups involved in the gold bio-reduction process. Influence of the volume of extract and concentration of gold (III) chloride trihydrate (HAuCl4.3H2O) on the synthesis of AuNPs were also investigated. The results obtained indicate potential optimization and functionalization of AuNPs for future applications in bionanotechnology especially in the field of medicine.

  4. Incorporating BDI Agents into Human-Agent Decision Making Research

    NASA Astrophysics Data System (ADS)

    Kamphorst, Bart; van Wissen, Arlette; Dignum, Virginia

    Artificial agents, people, institutes and societies all have the ability to make decisions. Decision making as a research area therefore involves a broad spectrum of sciences, ranging from Artificial Intelligence to economics to psychology. The Colored Trails (CT) framework is designed to aid researchers in all fields in examining decision making processes. It is developed both to study interaction between multiple actors (humans or software agents) in a dynamic environment, and to study and model the decision making of these actors. However, agents in the current implementation of CT lack the explanatory power to help understand the reasoning processes involved in decision making. The BDI paradigm that has been proposed in the agent research area to describe rational agents, enables the specification of agents that reason in abstract concepts such as beliefs, goals, plans and events. In this paper, we present CTAPL: an extension to CT that allows BDI software agents that are written in the practical agent programming language 2APL to reason about and interact with a CT environment.

  5. Solution-based synthesis and design of late transition metal chalcogenide materials for oxygen reduction reaction (ORR).

    PubMed

    Gao, Min-Rui; Jiang, Jun; Yu, Shu-Hong

    2012-01-09

    Late transition metal chalcogenide (LTMC) nanomaterials have been introduced as a promising Pt-free oxygen reduction reaction (ORR) electrocatalysts because of their low cost, good ORR activity, high methanol tolerance, and facile synthesis. Herein, an overview on the design and synthesis of LTMC nanomaterials by solution-based strategies is presented along with their ORR performances. Current solution-based synthetic approaches towards LTMC nanomaterials include a hydrothermal/solvothermal approach, single-source precursor approach, hot-injection approach, template-directed soft synthesis, and Kirkendall-effect-induced soft synthesis. Although the ORR activity and stability of LTMC nanomaterials are still far from what is needed for practical fuel-cell applications, much enhanced electrocatalytic performance can be expected. Recent advances have emphasized that decorating the surface of the LTMC nanostructures with other functional nanoparticles can lead to much better ORR catalytic activity. It is believed that new synthesis approaches to LTMCs, modification techniques of LTMCs, and LTMCs with desirable morphology, size, composition, and structures are expected to be developed in the future to satisfy the requirements of commercial fuel cells. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Electric power market agent design

    NASA Astrophysics Data System (ADS)

    Oh, Hyungseon

    The electric power industry in many countries has been restructured in the hope of a more economically efficient system. In the restructured system, traditional operating and planning tools based on true marginal cost do not perform well since information required is strictly confidential. For developing a new tool, it is necessary to understand offer behavior. The main objective of this study is to create a new tool for power system planning. For the purpose, this dissertation develops models for a market and market participants. A new model is developed in this work for explaining a supply-side offer curve, and several variables are introduced to characterize the curve. Demand is estimated using a neural network, and a numerical optimization process is used to determine the values of the variables that maximize the profit of the agent. The amount of data required for the optimization is chosen with the aid of nonlinear dynamics. To suggest an optimal demand-side bidding function, two optimization problems are constructed and solved for maximizing consumer satisfaction based on the properties of two different types of demands: price-based demand and must-be-served demand. Several different simulations are performed to test how an agent reacts in various situations. The offer behavior depends on locational benefit as well as the offer strategies of competitors.

  7. Macromolecular and Dendrimer Based Magnetic Resonance Contrast Agents

    PubMed Central

    Bumb, Ambika; Brechbiel, Martin W.; Choyke, Peter

    2010-01-01

    Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20–25 years, a number of gadolinium based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution and targeting of dendrimer-based MR contrast agents are also discussed. PMID:20590365

  8. Synthesis: Intertwining product and process

    NASA Technical Reports Server (NTRS)

    Weiss, David M.

    1990-01-01

    Synthesis is a proposed systematic process for rapidly creating different members of a program family. Family members are described by variations in their requirements. Requirements variations are mapped to variations on a standard design to generate production quality code and documentation. The approach is made feasible by using principles underlying design for change. Synthesis incorporates ideas from rapid prototyping, application generators, and domain analysis. The goals of Synthesis and the Synthesis process are discussed. The technology needed and the feasibility of the approach are also briefly discussed. The status of current efforts to implement Synthesis methodologies is presented.

  9. Performance Analysis and Design Synthesis (PADS) computer program. Volume 2: Program description, part 1

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The Performance Analysis and Design Synthesis (PADS) computer program has a two-fold purpose. It can size launch vehicles in conjunction with calculus-of-variations optimal trajectories and can also be used as a general-purpose branched trajectory optimization program. In the former use, it has the Space Shuttle Synthesis Program as well as a simplified stage weight module for optimally sizing manned recoverable launch vehicles. For trajectory optimization alone or with sizing, PADS has two trajectory modules. The first trajectory module uses the method of steepest descent; the second employs the method of quasilinearization, which requires a starting solution from the first trajectory module. For Volume 1 see N73-13199.

  10. A robust variable sampling time BLDC motor control design based upon μ-synthesis.

    PubMed

    Hung, Chung-Wen; Yen, Jia-Yush

    2013-01-01

    The variable sampling rate system is encountered in many applications. When the speed information is derived from the position marks along the trajectory, one would have a speed dependent sampling rate system. The conventional fixed or multisampling rate system theory may not work in these cases because the system dynamics include the uncertainties which resulted from the variable sampling rate. This paper derived a convenient expression for the speed dependent sampling rate system. The varying sampling rate effect is then translated into multiplicative uncertainties to the system. The design then uses the popular μ-synthesis process to achieve a robust performance controller design. The implementation on a BLDC motor demonstrates the effectiveness of the design approach.

  11. A Robust Variable Sampling Time BLDC Motor Control Design Based upon μ-Synthesis

    PubMed Central

    Yen, Jia-Yush

    2013-01-01

    The variable sampling rate system is encountered in many applications. When the speed information is derived from the position marks along the trajectory, one would have a speed dependent sampling rate system. The conventional fixed or multisampling rate system theory may not work in these cases because the system dynamics include the uncertainties which resulted from the variable sampling rate. This paper derived a convenient expression for the speed dependent sampling rate system. The varying sampling rate effect is then translated into multiplicative uncertainties to the system. The design then uses the popular μ-synthesis process to achieve a robust performance controller design. The implementation on a BLDC motor demonstrates the effectiveness of the design approach. PMID:24327804

  12. A redox-based mechanism for nitric oxide-induced inhibition of DNA synthesis in human vascular smooth muscle cells

    PubMed Central

    Bundy, Ruth E; Marczin, Nándor; Chester, Adrian H; Yacoub, Magdi

    2000-01-01

    The current study explored potential redox mechanisms of nitric oxide (NO)-induced inhibition of DNA synthesis in cultured human and rat aortic smooth muscle cells.Exposure to S-nitrosothiols, DETA-NONOate and NO itself inhibited ongoing DNA synthesis and S phase progression in a concentration-dependent manner, as measured by thymidine incorporation and flow cytometry. Inhibition by NO donors occurred by release of NO, as detected by chemiluminescence and judged by the effects of NO scavengers, haemoglobin and cPTIO.Co-incubation with redox compounds, N-acetyl-L-cysteine, glutathione and L-ascorbic acid prevented NO inhibition of DNA synthesis. These observations suggest that redox agents may alternatively attenuate NO bioactivity extracellularly, interfere with intracellular actions of NO on the DNA synthesis machinery or restore DNA synthesis after established inhibition by NO.Recovery of DNA synthesis after inhibition by NO was similar with and without redox agents suggesting that augmented restoration of DNA synthesis is an unlikely mechanism to explain redox regulation.Study of extracellular interactions revealed that all redox agents potentiated S-nitrosothiol decomposition and NO release.Examination of intracellular NO bioactivity showed that as opposed to attenuation of NO inhibition of DNA synthesis by redox agents, there was no inhibition (potentiation in the presence of ascorbic acid) of soluble guanylate cyclase (sGC) activation judged by cyclic GMP accumulation in rat cells.These data provide evidence that NO-induced inhibition of ongoing DNA synthesis is sensitive to redox environment. Redox processes might protect the DNA synthesis machinery from inhibition by NO, in the setting of augmented liberation of biologically active NO from NO donors. PMID:10742309

  13. Investigation of innovative synthesis of biologically active compounds on the basis of newly developed reactions.

    PubMed

    Honda, Toshio

    2012-01-01

    Synthesis of biologically active compounds, including natural products and pharmaceutical agents, is an important and interesting research area since the large structural diversity and complexity of bioactive compounds make them an important source of leads and scaffolds in drug discovery and development. Many structurally and also biologically interesting compounds, including marine natural products, have been isolated from nature and have also been prepared on the basis of a computational design for the purpose of developing medicinal chemistry. In order to obtain a wide variety of derivatives of biologically active compounds from the viewpoint of medicinal chemistry, it is essential to establish efficient synthetic procedures for desired targets. Newly developed reactions should also be used for efficient synthesis of desired compounds. Thus, recent progress in the synthesis of biologically active compounds by focusing on the development of new reactions is summarized in this review article.

  14. Benign by design: catalyst-free in-water, on-water green chemical methodologies in organic synthesis

    EPA Science Inventory

    The development of organic synthesis under sustainable conditions is a primary goal of practicing green chemists who want to prevent pollution and design safer pathways. Although, it is challenging to avoid the use of catalysts, or solvents in all the organic reactions but progre...

  15. Design and Control of Large Collections of Learning Agents

    NASA Technical Reports Server (NTRS)

    Agogino, Adrian

    2001-01-01

    The intelligent control of multiple autonomous agents is an important yet difficult task. Previous methods used to address this problem have proved to be either too brittle, too hard to use, or not scalable to large systems. The 'Collective Intelligence' project at NASA/Ames provides an elegant, machine-learning approach to address these problems. This approach mathematically defines some essential properties that a reward system should have to promote coordinated behavior among reinforcement learners. This work has focused on creating additional key properties and algorithms within the mathematics of the Collective Intelligence framework. One of the additions will allow agents to learn more quickly, in a more coordinated manner. The other will let agents learn with less knowledge of their environment. These additions will allow the framework to be applied more easily, to a much larger domain of multi-agent problems.

  16. Synthesis of silver nanoparticles using Dioscorea bulbifera tuber extract and evaluation of its synergistic potential in combination with antimicrobial agents

    PubMed Central

    Ghosh, Sougata; Patil, Sumersing; Ahire, Mehul; Kitture, Rohini; Kale, Sangeeta; Pardesi, Karishma; Cameotra, Swaranjit S; Bellare, Jayesh; Dhavale, Dilip D; Jabgunde, Amit; Chopade, Balu A

    2012-01-01

    . Conclusion This is the first report on the synthesis of silver nanoparticles using D. bulbifera tuber extract followed by an estimation of its synergistic potential for enhancement of the antibacterial activity of broad spectrum antimicrobial agents. PMID:22334779

  17. Synthesis of silver nanoparticles using Dioscorea bulbifera tuber extract and evaluation of its synergistic potential in combination with antimicrobial agents.

    PubMed

    Ghosh, Sougata; Patil, Sumersing; Ahire, Mehul; Kitture, Rohini; Kale, Sangeeta; Pardesi, Karishma; Cameotra, Swaranjit S; Bellare, Jayesh; Dhavale, Dilip D; Jabgunde, Amit; Chopade, Balu A

    2012-01-01

    the synthesis of silver nanoparticles using D. bulbifera tuber extract followed by an estimation of its synergistic potential for enhancement of the antibacterial activity of broad spectrum antimicrobial agents.

  18. Model-based synthesis of locally contingent responses to global market signals

    NASA Astrophysics Data System (ADS)

    Magliocca, N. R.

    2015-12-01

    Rural livelihoods and the land systems on which they depend are increasingly influenced by distant markets through economic globalization. Place-based analyses of land and livelihood system sustainability must then consider both proximate and distant influences on local decision-making. Thus, advancing land change theory in the context of economic globalization calls for a systematic understanding of the general processes as well as local contingencies shaping local responses to global signals. Synthesis of insights from place-based case studies of land and livelihood change is a path forward for developing such systematic knowledge. This paper introduces a model-based synthesis approach to investigating the influence of local socio-environmental and agent-level factors in mediating land-use and livelihood responses to changing global market signals. A generalized agent-based modeling framework is applied to six case-study sites that differ in environmental conditions, market access and influence, and livelihood settings. The largest modeled land conversions and livelihood transitions to market-oriented production occurred in sties with relatively productive agricultural land and/or with limited livelihood options. Experimental shifts in the distributions of agents' risk tolerances generally acted to attenuate or amplify responses to changes in global market signals. Importantly, however, responses of agents at different points in the risk tolerance distribution varied widely, with the wealth gap growing wider between agents with higher or lower risk tolerance. These results demonstrate model-based synthesis is a promising approach to overcome many of the challenges of current synthesis methods in land change science, and to identify generalized as well as locally contingent responses to global market signals.

  19. Pyrazole derivatives as antitumor, anti-inflammatory and antibacterial agents.

    PubMed

    Liu, Jia-Jia; Zhao, Meng-Yue; Zhang, Xin; Zhao, Xin; Zhu, Hai-Liang

    2013-11-01

    Within the past years, many researches on the synthesis, structure-activity relationships (SAR), antitumor, antiinflammatory and anti-bacterial activities of the pyrazole derivatives have been reported. Several pyrazole derivatives possess important pharmacological activities and they have been proved useful materials in drug research. Pyrazole derivatives play an important role in antitumor agents because of their good inhibitory activity against BRAF(V600E), EGFR, telomerase, ROS Receptor Tyrosine Kinase and Aurora-A kinase. In addition, pyrazole derivatives also show good antiinflammatory and anti-bacterial activities. In this review, the bioactivities of the pyrazole derivatives mentioned above will be summarized in detail. We sincerely hope that increasing knowledge of the SAR and cellular processes underlying the bioactivity of pyrazole derivatives will be beneficial to the rational design of new generation of small molecule drugs.

  20. Design and synthesis of organic-inorganic hybrid capsules for biotechnological applications.

    PubMed

    Shi, Jiafu; Jiang, Yanjun; Wang, Xiaoli; Wu, Hong; Yang, Dong; Pan, Fusheng; Su, Yanlei; Jiang, Zhongyi

    2014-08-07

    Organic-inorganic hybrid capsules, which typically possess a hollow lumen and a hybrid wall, have emerged as a novel and promising class of hybrid materials and have attracted enormous attention. In comparison to polymeric capsules or inorganic capsules, the hybrid capsules combine the intrinsic physical/chemical properties of the organic and inorganic moieties, acquire more degrees of freedom to manipulate multiple interactions, create hierarchical structures and integrate multiple functionalities. Thus, the hybrid capsules exhibit superior mechanical strength (vs. polymeric capsules) and diverse functionalities (vs. inorganic capsules), which may give new opportunities to produce high-performance materials. Much effort has been devoted to exploring innovative and effective methods for the synthesis of hybrid capsules that exhibit desirable performance in target applications. This tutorial review firstly presents a brief description of the capsular structure and hybrid materials in nature, then classifies the hybrid capsules into molecule-hybrid capsules and nano-hybrid capsules based upon the size of the organic and inorganic moieties in the capsule wall, followed by a detailed discussion of the design and synthesis of the hybrid capsules. For each kind of hybrid capsule, the state-of-the-art synthesis methods are described in detail and a critical comment is embedded. The applications of these hybrid capsules in biotechnological areas (biocatalysis, drug delivery, etc.) have also been summarized. Hopefully, this review will offer a perspective and guidelines for the future research and development of hybrid capsules.

  1. Discovery of novel taspine derivatives as antiangiogenic agents.

    PubMed

    Zhang, Jie; Zhang, Yanmin; Zhang, Sanqi; Wang, Sicen; He, Langchong

    2010-01-15

    VEGFR-2 plays a critical role in vasculogenesis and inhibitors of VEGFR-2 could be used in the treatment of cancer. Taspine was one of the active ingredients screened by using an endothelial cell membrane chromatography and showed inhibition against VEGFR-2. In our research, we explored how the lactone ring and biphenyl scaffold in taspine influence its potent in vitro anticancer and antiangiogenesis activities. Accordingly, we report the design, synthesis, and preliminary evaluation of four novel taspine derivatives as VEGFR-2 inhibitors. The preliminary biological test showed that one of the compounds showed much better inhibitory activities against CACO-2 (IC(50)=52.5nM) and ECV304 (IC(50)=2.67nM) than taspine. This result enlarges the interest in ring-opened taspine derivative skeleton in the search of new antiangiogenesis agents. Copyright 2009 Elsevier Ltd. All rights reserved.

  2. Applications of plant terpenoids in the synthesis of colloidal silver nanoparticles.

    PubMed

    Mashwani, Zia-Ur-Rehman; Khan, Mubarak Ali; Khan, Tariq; Nadhman, Akhtar

    2016-08-01

    Green chemistry is the design of chemical products and processes that reduce or eliminate the generation of hazardous substances. Since the last few years, natural products especially plant secondary metabolites have been extensively explored for their potency to synthesize silver nanoparticles (AgNPs). The plant-based AgNPs are safer, energy efficient, eco-friendly, and less toxic than chemically synthesized counterparts. The secondary metabolites, ubiquitously found in plants especially the terpenoid-rich essential oils, have a significant role in AgNPs synthesis. Terpenoids belong to the largest family of natural products and are found in all kinds of organisms. Their involvement in the synthesis of plant-based AgNPs has got much attention in the recent years. The current article is not meant to provide an exhaustive overview of green synthesis of nanoparticles, but to present the pertinent role of plant terpenoids in the biosynthesis of AgNPs, as capping and reducing agents for development of uniform size and shape AgNPs. An emphasis on the important role of FTIR in the identification and elucidation of major functional groups in terpenoids for AgNPs synthesis has also been reviewed in this manuscript. It was found that no such article is available that has discussed the role of plant terpenoids in the green synthesis of AgNPs. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Metal Ion-Catalyzed Alcoholysis as a Strategy for the High Loading Destruction of Chemical Warfare Organophosphorus Agents

    DTIC Science & Technology

    2013-11-01

    products was developed. At the core of the strategy was the use of the thionyl chloride reaction (shown above) for the synthesis of the G agent simulant...The synthesis diverges at the chloridate stage, where instead of conversion to the fluoride derivative, conversion to the mixed ester is accomplished...12 6.2 Synthesis of Product Standards ........................................................................14 6.3

  4. Potential therapeutic agents derived from the cannabinoid nucleus.

    PubMed

    Pars, H G; Howes, J F

    1977-01-01

    Drugs derived from Cannabis sativa (Cannabinceae) were used until the 1940's for their stimulant and depressant effects for treating somatic and psychiatric illnesses. Renewed interest in marihuana research began in the 1970's and again pointed to the therapeutic potential of cannabinoids. Safer and more useful therapeutic agents may be generated from cannabinoids similarly to morphine, lysergic acid diethylamide, and cocaine which have structurally related analgesics, oxytoxics, and local anesthetics respectively. It has been shown that the C-ring in cannabinoids can be substituted with a variety of nitrogen and sulfur-containing rings without loss of CNS (central nervous system) activity. Cannabinoids have been shown to inhibit prostaglandin synthesis, intensify pressor effects of endogenous amines like norepinephrine, and enhance the stimulant effects of amphetamine. Cannabinoids' therapeutic potential lies in the areas of analgesics and anticonvulsants, and for use as a sedative-hypnotic, an antiglaucoma agent, an antiasthmatic agent, an antidiarrheal agent, and possibly as an anticancer and immunosuppressant agent.

  5. Synthesis and biological evaluation of coumarin derivatives containing imidazole skeleton as potential antibacterial agents.

    PubMed

    Hu, Yang; Shen, Yufeng; Wu, Xiaohu; Tu, Xiao; Wang, Gao-Xue

    2018-01-01

    Emergence of multidrug-resistant bacteria causes an urgent need for new generation of antibiotics, which may have a different mechanism of inhibition or killing action from the existing. Here, we report on the design, synthesis, and biological evaluation of thirty-nine coumarin derivatives in order to solve the antibacterial resistance by targeting at the inhibition of biosynthesis pathway of fatty acids. Their antibacterial activities against Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, and Flavobacterium cloumnare are tested and action mechanism against the key enzyme in bacterial fatty acid synthesis pathway are studied. The results show that compounds 13 and 18 have potent and broad spectrum antimicrobial activity. In addition, 9, 14 and 19 show eminent antimicrobial efficacy toward S. aureus, S. agalactiae, and F. cloumnare. Mechanistically, coumarin derivatives display the antibacterial activity via the control of FabI and FabK function. The structure-activity relationship analysis indicate that the length of linker and imidazole substitute group could significantly influence the antimicrobial activity, as well as the inhibitory activity against FabI and FabK. The structural optimization analysis of coumarin suggest that derivatives 9, 13, 14, 18 and 19 could be a viable way of preventing and controlling bacteria and considered as promising lead compounds for the development of commercial drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. ROOM TEMPERATURE BULK SYNTHESIS OF SILVER NANOCABLES WRAPPED WITH POLYPYRROLE

    EPA Science Inventory

    Wet chemical synthesis of silver cables wrapped with polypyrrole is reported in aqueous media without use of any surfactant/capping agent and/or template. The method employs direct polymerization of pyrrole of an aqueous solution with AgNO3 as an oxidizing agent. The four probe c...

  7. N-acetylcysteine stimulates protein synthesis in enterocytes independently of glutathione synthesis.

    PubMed

    Yi, Dan; Hou, Yongqing; Wang, Lei; Long, Minhui; Hu, Shengdi; Mei, Huimin; Yan, Liqiong; Hu, Chien-An Andy; Wu, Guoyao

    2016-02-01

    Dietary supplementation with N-acetylcysteine (NAC) has been reported to improve intestinal health and treat gastrointestinal diseases. However, the underlying mechanisms are not fully understood. According to previous reports, NAC was thought to exert its effect through glutathione synthesis. This study tested the hypothesis that NAC enhances enterocyte growth and protein synthesis independently of cellular glutathione synthesis. Intestinal porcine epithelial cells were cultured for 3 days in Dulbecco's modified Eagle medium containing 0 or 100 μM NAC. To determine a possible role for GSH (the reduced form of glutathione) in mediating the effect of NAC on cell growth and protein synthesis, additional experiments were conducted using culture medium containing 100 μM GSH, 100 μM GSH ethyl ester (GSHee), diethylmaleate (a GSH-depletion agent; 10 μM), or a GSH-synthesis inhibitor (buthionine sulfoximine, BSO; 20 μM). NAC increased cell proliferation, GSH concentration, and protein synthesis, while inhibiting proteolysis. GSHee enhanced cell proliferation and GSH concentration without affecting protein synthesis but inhibited proteolysis. Conversely, BSO or diethylmaleate reduced cell proliferation and GSH concentration without affecting protein synthesis, while promoting protein degradation. At the signaling level, NAC augmented the protein abundance of total mTOR, phosphorylated mTOR, and phosphorylated 70S6 kinase as well as mRNA levels for mTOR and p70S6 kinase in IPEC-1 cells. Collectively, these results indicate that NAC upregulates expression of mTOR signaling proteins to stimulate protein synthesis in enterocytes independently of GSH generation. Our findings provide a hitherto unrecognized biochemical mechanism for beneficial effects of NAC in intestinal cells.

  8. Design, synthesis and structure-activity relationship study of wollamide B; a new potential anti TB agent

    PubMed Central

    Laqua, Katja; Walkowska, Anna Maria; Cunningham, Fraser; Martinez-Martinez, Maria Santos; Cuevas-Zurita, Juan Carlos; Ballell-Pages, Lluís; Imming, Peter

    2017-01-01

    Wollamide B is a cationic antimycobacterial cyclohexapeptide that exhibits activity against Mycobacterium bovis (M. bovis) (IC50 of 3.1 μM). Aiming to define its structural activity relationship (SAR), optimizing potency and pharmacokinetic properties, libraries of analogues were synthesized following a standard Fmoc-based solid phase peptide synthesis approach. The antimycobacterial activities of wollamide B and all the synthesized analogues were tested against Mycobacterium tuberculosis (Mtb) H37Rv. Parallely, in vitro drug metabolism and pharmacokinetic (ADME) profiling was done for the synthesized compounds to evaluate their drug likeness. Among the 25 synthesized wollamides five of them showed potent activities with MICs ≤ 3.1 μM and found to be nontoxic against human HepG2 cells up to 100 μM. The results of the in vitro ADME profiling revealed the remarkable plasma stability and very good aqueous solubility of the class in general while the metabolic stability was found to be moderate to low. Of particular note, compounds 7c (MIC = 1.1 μM) and 13c (0.6 μM) that exhibited good balance of antimycobacterial activity vs. optimal pharmacokinetic properties could be used as a new lead for further development. PMID:28423019

  9. Crucial breakthrough of second near-infrared biological window fluorophores: design and synthesis toward multimodal imaging and theranostics

    DOE PAGES

    He, Shuqing; Song, Jun; Qu, Junle; ...

    2018-01-01

    Recent advances in the chemical design and synthesis of fluorophores in the second near-infrared biological window (NIR-II) for multimodal imaging and theranostics are summarized and highlighted in this review article.

  10. Crucial breakthrough of second near-infrared biological window fluorophores: design and synthesis toward multimodal imaging and theranostics

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

    He, Shuqing; Song, Jun; Qu, Junle

    Recent advances in the chemical design and synthesis of fluorophores in the second near-infrared biological window (NIR-II) for multimodal imaging and theranostics are summarized and highlighted in this review article.

  11. Green route for synthesis of multifunctional fluorescent carbon dots from Tulsi leaves and its application as Cr(VI) sensors, bio-imaging and patterning agents.

    PubMed

    Bhatt, Shreya; Bhatt, Madhuri; Kumar, Anshu; Vyas, Gaurav; Gajaria, Tejal; Paul, Parimal

    2018-07-01

    We report a one pot green strategy for the synthesis of carbon dots using tulsi leaves and their potential application in sensing of Cr(VI) selectively. The detection mechanism is based on the phenomenon called inner filter effect (IFE) and a good linear static quenching was observed in the range of 1.6 μM to 50 μM with a detection limit of 4.5 ppb. The reversible switching in fluorescence has been tested and a good recovery in fluorescence was observed up to three consecutive cycles upon addition of ascorbic acid as reducing agent. Also the low toxicity, high fluorescence and photostabilty of the CDs make them excellent imaging and patterning agent. The acid and alkali resistant property of these CDs makes it suitable for real sample analysis. The fluorescent CDs were applied for successful detection of Cr(VI) in water with spike-recoveries ranging from 93 to 99%. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Α-aryl-N-alkyl nitrones, as potential agents for stroke treatment: synthesis, theoretical calculations, antioxidant, anti-inflammatory, neuroprotective, and brain-blood barrier permeability properties.

    PubMed

    Chioua, Mourad; Sucunza, David; Soriano, Elena; Hadjipavlou-Litina, Dimitra; Alcázar, Alberto; Ayuso, Irene; Oset-Gasque, María Jesús; González, María Pilar; Monjas, Leticia; Rodríguez-Franco, María Isabel; Marco-Contelles, José; Samadi, Abdelouahid

    2012-01-12

    We report the synthesis, theoretical calculations, the antioxidant, anti-inflammatory, and neuroprotective properties, and the ability to cross the blood-brain barrier (BBB) of (Z)-α-aryl and heteroaryl-N-alkyl nitrones as potential agents for stroke treatment. The majority of nitrones compete with DMSO for hydroxyl radicals, and most of them are potent lipoxygenase inhibitors. Cell viability-related (MTT assay) studies clearly showed that nitrones 1-3 and 10 give rise to significant neuroprotection. When compounds 1-11 were tested for necrotic cell death (LDH release test) nitrones 1-3, 6, 7, and 9 proved to be neuroprotective agents. In vitro evaluation of the BBB penetration of selected nitrones 1, 2, 10, and 11 using the PAMPA-BBB assay showed that all of them cross the BBB. Permeable quinoline nitrones 2 and 3 show potent combined antioxidant and neuroprotective properties and, therefore, can be considered as new lead compounds for further development in specific tests for potential stroke treatment.

  13. Synthesis and pharmacokinetics of valopicitabine (NM283), an efficient prodrug of the potent anti-HCV agent 2'-C-methylcytidine.

    PubMed

    Pierra, Claire; Amador, Agnès; Benzaria, Samira; Cretton-Scott, Erika; D'Amours, Marc; Mao, John; Mathieu, Steven; Moussa, Adel; Bridges, Edward G; Standring, David N; Sommadossi, Jean-Pierre; Storer, Richard; Gosselin, Gilles

    2006-11-02

    In our search for new therapeutic agents against chronic hepatitis C, a ribonucleoside analogue, 2'-C-methylcytidine, was discovered to be a potent and selective inhibitor in cell culture of a number of RNA viruses, including the pestivirus bovine viral diarrhea virus, a surrogate model for hepatitis C virus (HCV), and three flaviviruses, namely, yellow fever virus, West Nile virus, and dengue-2 virus. However, pharmacokinetic studies revealed that 2'-C-methylcytidine suffers from a low oral bioavailability. To overcome this limitation, we have synthesized the 3'-O-l-valinyl ester derivative (dihydrochloride form, valopicitabine, NM283) of 2'-C-methylcytidine. We detail herein for the first time the chemical synthesis and physicochemical characteristics of this anti-HCV prodrug candidate, as well as a comparative study of its pharmacokinetic parameters with those of its parent nucleoside analogue, 2'-C-methylcytidine.

  14. Functional copolymer/organo-MMT nanoarchitectures. VI. Synthesis and characterization of novel nanocomposites by interlamellar controlled/living radical copolymerization via preintercalated RAFT-agent/organoclay complexes.

    PubMed

    Rzayev, Zakir M O; Söylemez, A Ernur

    2011-04-01

    We have developed a new approach for the synthesis of polymer nanocomposites using a bifunctional reversible addition-fragmentation chain transfer (RAFT) agent, two types of organo-montmorillonites, such as a non-reactive dimethyldodecyl ammonium (DMDA)-MMT and a reactive octadecylamine (ODA)-MMT organoclays, and a radical initiator. The method includes the following stages: (1) synthesis of RAFT intercalated O-MMTs by a physical or chemical interaction of the RAFT agent having two pendant carboxylic groups [S,S-bis(alpha,alpha'-dimethyl-alpha"-acetic acid)trithiocarbonate] with surface alkyl amines of O-MMT containing tertiary ammonium cation or primary amine groups through strong H-bonding and complexing/amidization reactions, respectively, and (2) utilization of these well-dispersed and intercalated RAFT ... O-MMT complexes and their amide derivatives as new modified RAFT agents in radical-initiated interlamellar controlled/living copolymerization of itaconic acid (IA)-n-butylmethacrylate (BMA) monomer pair. The structure and compositions of the synthesized RAFT ... O-MMT complexes and functional copolymer/O-MMT hybrids were confirmed by FTIR, XRD, thermal (DSC-TGA), SEM and TEM morphology analyses. It was demonstrated that the degree of interaction/exfoliation, morphology and thermal behavior of nanocomposites significantly depended on the type of organoclay and in situ interaction, as well as on the content of flexible butyl-ester linkages as a internal plasticizer. The results of the comparative analysis of the nanocomposites structure-composition-property relations show that the functional copolymer-organoclay hybrids prepared with reactive RAFT ... ODA-MMT complex and containing a combination of partially intercalated and predominantly exfoliated nano-structures exhibit relatively higher thermal stability and fine dispersed morphology. These effects were explained by in situ interfacial chemical reactions through amidization of RAFT with surface alkyl amine

  15. The synthesis of glutamic acid in the absence of enzymes: Implications for biogenesis

    NASA Technical Reports Server (NTRS)

    Morowitz, Harold; Peterson, Eta; Chang, Sherwood

    1995-01-01

    This paper reports on the non-enzymatic aqueous phase synthesis of amino acids from keto acids, ammonia and reducing agents. The facile synthesis of key metabolic intermediates, particularly in the glycolytic pathway, the citric acid cycle, and the first step of amino acid synthesis, lead to new ways of looking at the problem of biogenesis.

  16. Design of Enzymatically Cleavable Prodrugs of a Potent Platinum-Containing Anticancer Agent

    PubMed Central

    Ding, Song; Pickard, Amanda J.; Kucera, Gregory L.

    2014-01-01

    Using a versatile synthetic approach, a new class of potential ester prodrugs of highly potent, but systemically too toxic, platinum–acridine anticancer agents was generated. The new hybrids contain a hydroxyl group, which has been masked with a cleavable lipophilic acyl moiety. Both butanoic (butyric) and bulkier 2-propanepentanoic (valproic) esters were introduced. The goals of this design were to improve the drug-like properties (e.g., logD) and to reduce the systemic toxicity of the pharmacophore. Two distinct pathways by which the target compounds undergo effective ester hydrolysis, the proposed activating step, have been confirmed: platinum-assisted, self-immolative ester cleavage in a low-chloride environment (LC-ESMS, NMR spectroscopy) and enzymatic cleavage by human carboxylesterase-2 (hCES-2) (LC-ESMS). The valproic acid ester derivatives are the first example of a metal-containing agent cleavable by the pro-drug-converting enzyme. They show excellent chemical stability and reduced systemic toxicity. Preliminary results from screening in lung adenocarcinoma cell lines (A549, NCI-H1435) suggest that the mechanism of the valproic esters may involve intracellular deesterification. PMID:25303639

  17. Novel Cleanup Agents Designed Exclusively for Oil Field Membrane Filtration Systems Low Cost Field Demonstrations of Cleanup Agents in Controlled Experimental Environments

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

    David Burnett; Harold Vance

    2007-08-31

    The goal of our project is to develop innovative processes and novel cleaning agents for water treatment facilities designed to remove fouling materials and restore micro-filter and reverse osmosis (RO) membrane performance. This project is part of Texas A&M University's comprehensive study of the treatment and reuse of oilfield brine for beneficial purposes. Before waste water can be used for any beneficial purpose, it must be processed to remove contaminants, including oily wastes such as residual petroleum hydrocarbons. An effective way of removing petroleum from brines is the use of membrane filters to separate oily waste from the brine. Texasmore » A&M and its partners have developed highly efficient membrane treatment and RO desalination for waste water including oil field produced water. We have also developed novel and new cleaning agents for membrane filters utilizing environmentally friendly materials so that the water from the treatment process will meet U.S. EPA drinking water standards. Prototype micellar cleaning agents perform better and use less clean water than alternate systems. While not yet optimized, the new system restores essentially complete membrane flux and separation efficiency after cleaning. Significantly the amount of desalinated water that is required to clean the membranes is reduced by more than 75%.« less

  18. Ribozyme-mediated cleavage of c-fos mRNA reduces gene expression of DNA synthesis enzymes and metallothionein.

    PubMed Central

    Scanlon, K J; Jiao, L; Funato, T; Wang, W; Tone, T; Rossi, J J; Kashani-Sabet, M

    1991-01-01

    The c-fos gene product Fos has been implicated in many cellular processes, including signal transduction, DNA synthesis, and resistance to antineoplastic agents. A fos ribozyme (catalytic RNA) was designed to evaluate the effects of suppressing Fos protein synthesis on expression of enzymes involved in DNA synthesis, DNA repair, and drug resistance. DNA encoding the fos ribozyme (fosRb) was cloned into the pMAMneo expression plasmid, and the resultant vector was transfected into A2780DDP cells resistant to the chemotherapeutic agent cisplatin. The parental drug-sensitive A2780S cells were transfected with the pMMV vector containing the c-fos gene. Morphological alterations were accompanied by significant changes in pharmacological sensitivity in both c-fos- and fosRb-transfected cells. pMAMneo fosRb transfectants revealed decreased c-fos gene expression, concomitant with reduced thymidylate (dTMP) synthase, DNA polymerase beta, topoisomerase I, and metallothionein IIA mRNAs. In contrast, c-myc expression was elevated after fos ribozyme action. Insertion of a mutant ribozyme, mainly capable of antisense activity, into A2780DDP cells resulted in smaller reductions in c-fos gene expression and in cisplatin resistance than the active ribozyme. These studies establish a role for c-fos in drug resistance and in mediating DNA synthesis and repair processes by modulating expression of genes such as dTMP synthase, DNA polymerase beta, and topoisomerase I. These studies also suggest the utility of ribozymes in the analysis of cellular gene expression. Images PMID:1660142

  19. Plant mediated green synthesis: modified approaches.

    PubMed

    Das, Ratul Kumar; Brar, Satinder Kaur

    2013-11-07

    Plant mediated green synthesis of different metallic nanoparticles has emerged as one of the options for implementation of green chemistry principles, and successfully made an important contribution towards green nanotechnology. However, beyond the synthesis and application aspects, the science of green synthesis has carried some wrong perceptions in an unforeseen fashion. In this review, some of the key issues related to the green synthesis of metallic nanoparticles employing plants as reducing/capping agents have been addressed. Random selection of plants and its overall impact on the different aspects of green synthesis have been discussed. Emphasis is given to the setting of some standard selection criteria to be adopted for selecting a plant for use in green synthesis. How selection of a plant can positively or negatively influence both procedure and products of a green synthesis process is the prime concern of this article. In addition to selection, the key issue of biocompatibility associated with green synthesized metallic nanoparticles has been considered. Both selection of plant and biocompatibility were reconsidered for their minute details in terms of synthesis, analysis and data interpretation in the green synthesis approach. The key factors capable of fine tuning the core meaning of "green" in the synthesis of any metallic nanoparticles were taken into consideration. This article is an effort towards keeping the core meaning of green synthesis.

  20. 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

  1. 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.

  2. Global analysis of protein folding using massively parallel design, synthesis and testing

    PubMed Central

    Rocklin, Gabriel J.; Chidyausiku, Tamuka M.; Goreshnik, Inna; Ford, Alex; Houliston, Scott; Lemak, Alexander; Carter, Lauren; Ravichandran, Rashmi; Mulligan, Vikram K.; Chevalier, Aaron; Arrowsmith, Cheryl H.; Baker, David

    2017-01-01

    Proteins fold into unique native structures stabilized by thousands of weak interactions that collectively overcome the entropic cost of folding. Though these forces are “encoded” in the thousands of known protein structures, “decoding” them is challenging due to the complexity of natural proteins that have evolved for function, not stability. Here we combine computational protein design, next-generation gene synthesis, and a high-throughput protease susceptibility assay to measure folding and stability for over 15,000 de novo designed miniproteins, 1,000 natural proteins, 10,000 point-mutants, and 30,000 negative control sequences, identifying over 2,500 new stable designed proteins in four basic folds. This scale—three orders of magnitude greater than that of previous studies of design or folding—enabled us to systematically examine how sequence determines folding and stability in uncharted protein space. Iteration between design and experiment increased the design success rate from 6% to 47%, produced stable proteins unlike those found in nature for topologies where design was initially unsuccessful, and revealed subtle contributions to stability as designs became increasingly optimized. Our approach achieves the long-standing goal of a tight feedback cycle between computation and experiment, and promises to transform computational protein design into a data-driven science. PMID:28706065

  3. Formal Assurance for Cognitive Architecture Based Autonomous Agent

    NASA Technical Reports Server (NTRS)

    Bhattacharyya, Siddhartha; Eskridge, Thomas; Neogi, Natasha; Carvalho, Marco

    2017-01-01

    Autonomous systems are designed and deployed in different modeling paradigms. These environments focus on specific concepts in designing the system. We focus our effort in the use of cognitive architectures to design autonomous agents to collaborate with humans to accomplish tasks in a mission. Our research focuses on introducing formal assurance methods to verify the behavior of agents designed in Soar, by translating the agent to the formal verification environment Uppaal.

  4. Gadolinium-Based Contrast Agents for MR Cancer Imaging

    PubMed Central

    Zhou, Zhuxian; Lu, Zheng-Rong

    2013-01-01

    Magnetic resonance imaging (MRI) is a clinical imaging modality effective for anatomical and functional imaging of diseased soft tissues, including solid tumors. MRI contrast agents have been routinely used for detecting tumor at an early stage. Gadolinium based contrast agents are the most commonly used contrast agents in clinical MRI. There have been significant efforts to design and develop novel Gd(III) contrast agents with high relaxivity, low toxicity and specific tumor binding. The relaxivity of the Gd(III) contrast agents can be increased by proper chemical modification. The toxicity of Gd(III) contrast agents can be reduced by increasing the agents’ thermodynamic and kinetic stability, as well as optimizing their pharmacokinetic properties. The increasing knowledge in the field of cancer genomics and biology provides an opportunity for designing tumor-specific contrast agents. Various new Gd(III) chelates have been designed and evaluated in animal models for more effective cancer MRI. This review outlines the design and development, physicochemical properties, and in vivo properties of several classes of Gd(III)-based MR contrast agents for tumor imaging. PMID:23047730

  5. Exploration of the Maximum Entropy/Optimal Projection Approach to Control Design Synthesis for Large Space Structures.

    DTIC Science & Technology

    1985-02-01

    Energy Analysis , a branch of dynamic modal analysis developed for analyzing acoustic vibration problems, its present stage of development embodies a...Maximum Entropy Stochastic Modelling and Reduced-Order Design Synthesis is a rigorous new approach to this class of problems. Inspired by Statistical

  6. Progress in the development of gelling agents for improved culturability of microorganisms

    PubMed Central

    Das, Nabajit; Tripathi, Naveen; Basu, Srijoni; Bose, Chandra; Maitra, Susmit; Khurana, Sukant

    2015-01-01

    Gelling agents are required for formulating both solid and semisolid media, vital for the isolation of microorganisms. Gelatin was the first gelling agent to be discovered but it soon paved the way for agar, which has far superior material qualities. Source depletion, issues with polymerase-chain-reaction and inability to sustain extermophiles etc., necessitate the need of other gelling agents. Many new gelling agents, such as xantham gum, gellan gum, carrageenan, isubgol, and guar gum have been formulated, raising the hopes for the growth of previously unculturable microorganisms. We evaluate the progress in the development of gelling agents, with the hope that our synthesis would help accelerate research in the field. PMID:26257708

  7. NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A-T phosphoramidite building blocks.

    PubMed

    Schmidtgall, Boris; Höbartner, Claudia; Ducho, Christian

    2015-01-01

    Modifications of the nucleic acid backbone are essential for the development of oligonucleotide-derived bioactive agents. The NAA-modification represents a novel artificial internucleotide linkage which enables the site-specific introduction of positive charges into the otherwise polyanionic backbone of DNA oligonucleotides. Following initial studies with the introduction of the NAA-linkage at T-T sites, it is now envisioned to prepare NAA-modified oligonucleotides bearing the modification at X-T motifs (X = A, C, G). We have therefore developed the efficient and stereoselective synthesis of NAA-linked 'dimeric' A-T phosphoramidite building blocks for automated DNA synthesis. Both the (S)- and the (R)-configured NAA-motifs were constructed with high diastereoselectivities to furnish two different phosphoramidite reagents, which were employed for the solid phase-supported automated synthesis of two NAA-modified DNA oligonucleotides. This represents a significant step to further establish the NAA-linkage as a useful addition to the existing 'toolbox' of backbone modifications for the design of bioactive oligonucleotide analogues.

  8. Design and Synthesis of Cannabinoid 1 Receptor (CB1R) Allosteric Modulators: Drug Discovery Applications.

    PubMed

    Kulkarni, Abhijit R; Garai, Sumanta; Janero, David R; Thakur, Ganesh A

    2017-01-01

    Also expressed in various peripheral tissues, the type-1 cannabinoid receptor (CB1R) is the predominant G protein-coupled receptor (GPCR) in brain, where it is responsible for retrograde control of neurotransmitter release. Cellular signaling mediated by CB1R is involved in numerous physiological processes, and pharmacological CB1R modulation is considered a tenable therapeutic approach for diseases ranging from substance-use disorders and glaucoma to metabolic syndrome. Despite the design and synthesis of a variety of bioactive small molecules targeted to the CB1R orthosteric ligand-binding site, the potential of CB1R as a therapeutic GPCR has been largely unrealized due to adverse events associated with typical orthosteric CB1R agonists and antagonists/inverse agonists. Modulation of CB1R-mediated signal transmission by targeting alternative allosteric ligand-binding site(s) on the receptor has garnered interest as a potentially safer and more effective therapeutic modality. This chapter highlights the design and synthesis of novel, pharmacologically active CB1R allosteric modulators and emphasizes how their molecular properties and the positive and negative allosteric control they exert can lead to improved CB1R-targeted pharmacotherapeutics, as well as designer covalent probes that can be used to map CB1R allosteric binding domains and inform structure-based drug design. © 2017 Elsevier Inc. All rights reserved.

  9. Research on Intelligent Synthesis Environments

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K.; Lobeck, William E.

    2002-01-01

    Four research activities related to Intelligent Synthesis Environment (ISE) have been performed under this grant. The four activities are: 1) non-deterministic approaches that incorporate technologies such as intelligent software agents, visual simulations and other ISE technologies; 2) virtual labs that leverage modeling, simulation and information technologies to create an immersive, highly interactive virtual environment tailored to the needs of researchers and learners; 3) advanced learning modules that incorporate advanced instructional, user interface and intelligent agent technologies; and 4) assessment and continuous improvement of engineering team effectiveness in distributed collaborative environments.

  10. Research on Intelligent Synthesis Environments

    NASA Astrophysics Data System (ADS)

    Noor, Ahmed K.; Loftin, R. Bowen

    2002-12-01

    Four research activities related to Intelligent Synthesis Environment (ISE) have been performed under this grant. The four activities are: 1) non-deterministic approaches that incorporate technologies such as intelligent software agents, visual simulations and other ISE technologies; 2) virtual labs that leverage modeling, simulation and information technologies to create an immersive, highly interactive virtual environment tailored to the needs of researchers and learners; 3) advanced learning modules that incorporate advanced instructional, user interface and intelligent agent technologies; and 4) assessment and continuous improvement of engineering team effectiveness in distributed collaborative environments.

  11. Design, microwave-mediated synthesis and biological evaluation of novel 4-aryl(alkyl)amino-3-nitroquinoline and 2,4-diaryl(dialkyl)amino-3-nitroquinolines as anticancer agents.

    PubMed

    Chauhan, Monika; Rana, Anil; Alex, Jimi Marin; Negi, Arvind; Singh, Sandeep; Kumar, Raj

    2015-02-01

    Design, microwave-assisted synthesis of novel 4-aryl (alkyl)amino-3-nitroquinoline (1a-1l) and 2,4-diaryl (dialkyl)amino-3-nitroquinolines (2a-2k and 3a) via regioselective and complete nucleophilic substitution of 2,4-dichloro-3-nitroquinoline, respectively in water are presented. The newly synthesized compounds were evaluated for the first time for antiproliferative activity against EGFR overexpressing human lung (A-549 and H-460) and colon (HCT-116-wild type and HCT-116-p53 null) cancer cell lines. Some notions about structure-activity relationships (SAR) are presented. Compounds 2e, 2f, 2j and 3a overall exhibited excellent anticancer activity comparable to erlotinib which was used as a positive control. Molecular modeling studies disclosed the recognition pattern of the compounds and also supported the observed SAR. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Green Chemistry Approach for Synthesis of Effective Anticancer Palladium Nanoparticles.

    PubMed

    Gurunathan, Sangiliyandi; Kim, EunSu; Han, Jae Woong; Park, Jung Hyun; Kim, Jin-Hoi

    2015-12-15

    The purpose of this study was to design and synthesize Palladium nanoparticles (PdNPs) using an environmentally friendly approach and evaluate the in vitro efficacy of PdNPs in human ovarian cancer A2780 cells. Ultraviolet-Visible (UV-Vis) spectroscopy was used to monitor the conversion of Pd(II) ions to Pd(0)NPs. X-ray diffraction (XRD) revealed the crystallinity of the as-synthesized PdNPs and Fourier transform infrared spectroscopy (FTIR) further confirmed the role of the leaf extract of Evolvulus alsinoides as a reducing and stabilizing agent for the synthesis of PdNPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) showed that the average size of the NPs was 5 nm. After a 24-h exposure to PdNPs, cell viability and light microscopy assays revealed the dose-dependent toxicity of the PdNPs. Furthermore, the dose-dependent cytotoxicity of the PdNPs was confirmed by lactate dehydrogenase (LDH), increased reactive oxygen species (ROS) generation, activation of PdNPs-induced autophagy, impairment of mitochondrial membrane potential (MMP), enhanced caspase-3 activity, and detection of TUNEL-positive cells. Our study demonstrates a single, simple, dependable and green approach for the synthesis of PdNPs using leaf extracts of Evolvulus alsinoides. Furthermore, the in vitro efficacy of PdNPs in human ovarian cancer cells suggests that it could be an effective therapeutic agent for cancer therapy.

  13. Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.

    PubMed

    Nojima, Kuniharu; Hochegger, Helfrid; Saberi, Alihossein; Fukushima, Toru; Kikuchi, Koji; Yoshimura, Michio; Orelli, Brian J; Bishop, Douglas K; Hirano, Seiki; Ohzeki, Mioko; Ishiai, Masamichi; Yamamoto, Kazuhiko; Takata, Minoru; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Yamazoe, Mitsuyoshi; Kawamoto, Takuo; Araki, Kasumi; Takahashi, Jun A; Hashimoto, Nobuo; Takeda, Shunichi; Sonoda, Eiichiro

    2005-12-15

    Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair pathways is distinctively different from the situation in yeast, where NER seems to play a major role in dealing with ICL. Cells deficient in Rev3, the catalytic subunit of TLS polymerase Polzeta, showed the highest sensitivity to cisplatin followed by fanc-c. Furthermore, epistasis analysis revealed that these two mutants work in the same pathway. Our genetic comprehensive study reveals a critical role for DNA repair pathways that release DNA replication block at ICLs in cellular tolerance to cross-linking agents and could be directly exploited in designing an effective chemotherapy.

  14. Synthesis of Pt 3Y and Other Early–Late Intermetallic Nanoparticles by Way of a Molten Reducing Agent

    DOE PAGES

    Kanady, Jacob S.; Leidinger, Peter; Haas, Andreas; ...

    2017-03-29

    Early–late intermetallic phases have garnered increased attention recently for their catalytic properties. To achieve the high surface areas needed for industrially relevant applications, these phases must be synthesized as nanoparticles in a scalable fashion. Herein, Pt 3Y—targeted as a prototypical example of an early–late intermetallic—has been synthesized as nanoparticles approximately 5–20 nm in diameter via a solution process and characterized by XRD, TEM, EDS, and XPS. The key development is the use of a molten borohydride (MEt 3BH, M = Na, K) as both the reducing agent and reaction medium. Readily available halide precursors of the two metals are used.more » Accordingly, no organic ligands are necessary, as the resulting halide salt byproduct prevents sintering, which further permits dispersion of the nanoscale intermetallic onto a support. The versatility of this approach was validated by the synthesis of other intermetallic phases such as Pt 3Sc, Pt 3Lu, Pt 2Na, and Au 2Y.« less

  15. Synthesis of Pt 3Y and Other Early–Late Intermetallic Nanoparticles by Way of a Molten Reducing Agent

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

    Kanady, Jacob S.; Leidinger, Peter; Haas, Andreas

    Early–late intermetallic phases have garnered increased attention recently for their catalytic properties. To achieve the high surface areas needed for industrially relevant applications, these phases must be synthesized as nanoparticles in a scalable fashion. Herein, Pt 3Y—targeted as a prototypical example of an early–late intermetallic—has been synthesized as nanoparticles approximately 5–20 nm in diameter via a solution process and characterized by XRD, TEM, EDS, and XPS. The key development is the use of a molten borohydride (MEt 3BH, M = Na, K) as both the reducing agent and reaction medium. Readily available halide precursors of the two metals are used.more » Accordingly, no organic ligands are necessary, as the resulting halide salt byproduct prevents sintering, which further permits dispersion of the nanoscale intermetallic onto a support. The versatility of this approach was validated by the synthesis of other intermetallic phases such as Pt 3Sc, Pt 3Lu, Pt 2Na, and Au 2Y.« less

  16. Mesquite Gum as a Novel Reducing and Stabilizing Agent for Modified Tollens Synthesis of Highly Concentrated Ag Nanoparticles

    PubMed Central

    Moreno-Trejo, Maira Berenice; Sánchez-Domínguez, Margarita

    2016-01-01

    The synthesis that is described in this study is for the preparation of silver nanoparticles of sizes ranging from 10 nm to 30 nm with a defined shape (globular), confirmed by UV-vis, SEM, STEM and DLS analysis. This simple and favorable one-step modified Tollens reaction does not require any special equipment or other stabilizing or reducing agent except for a solution of purified mesquite gum, and it produces aqueous colloidal dispersions of silver nanoparticles with a stability that exceeds three months, a relatively narrow size distribution, a low tendency to aggregate and a yield of at least 95% for all cases. Reaction times are between 15 min and 60 min to obtain silver nanoparticles in concentrations ranging from 0.1 g to 3 g of Ag per 100 g of reaction mixture. The proposed synthetic method presents a high potential for scale-up, since its production capacity is rather high and the methodology is simple. PMID:28773938

  17. Delay-dependent coupling for a multi-agent LTI consensus system with inter-agent delays

    NASA Astrophysics Data System (ADS)

    Qiao, Wei; Sipahi, Rifat

    2014-01-01

    Delay-dependent coupling (DDC) is considered in this paper in a broadly studied linear time-invariant multi-agent consensus system in which agents communicate with each other under homogeneous delays, while attempting to reach consensus. The coupling among the agents is designed here as an explicit parameter of this delay, allowing couplings to autonomously adapt based on the delay value, and in order to guarantee stability and a certain degree of robustness in the network despite the destabilizing effect of delay. Design procedures, analysis of convergence speed of consensus, comprehensive numerical studies for the case of time-varying delay, and limitations are presented.

  18. Panax ginseng induces human Type I collagen synthesis through activation of Smad signaling.

    PubMed

    Lee, Jongsung; Jung, Eunsun; Lee, Jiyoung; Huh, Sungran; Kim, Jieun; Park, Mijung; So, Jungwoon; Ham, Younggeun; Jung, Kwangseon; Hyun, Chang-Gu; Kim, Yeong Shik; Park, Deokhoon

    2007-01-03

    Skin aging appears to be principally related to a decrease in levels of Type I collagen, the primary component of the dermal layer of skin. It is important to introduce an efficient agent for effective management of skin aging; this agent should have the fewest possible side effects and the greatest wrinkle-reducing effect. In the course of screening collagen production-promoting agents, we obtained Panax ginseng C.A. Meyer. This study was designed to investigate the possible collagen production-promoting activities of Panax ginseng C.A. Meyer root extract (PGRE) in human dermal fibroblast cells. As a first step to this end, human COL1A2 promoter luciferase assay was performed in human dermal fibroblast cells. In this assay, PGRE activated human COL1A2 promoter activity in a concentration-dependent manner. Human Type I procollagen synthesis was also induced by PGRE. These results suggest that PGRE promotes collagen production in human dermal fibroblast cells. Additionally, we have attempted to characterize the mechanism of action of PGRE in Type I procollagen synthesis. PGRE was found to induce the phosphorylation of Smad2, an important transcription factor in the production of Type I procollagen. When applied topically in a human skin primary irritation test, PGRE did not induce any adverse reactions. Therefore, based on these results, we suggest the possibility that PGRE may be considered as an attractive, wrinkle-reducing candidate for topical application.

  19. Ultrasound Contrast Agents

    NASA Astrophysics Data System (ADS)

    Cachard, Christian; Basset, Olivier

    While the use of contrast agents in other imaging modalities (X ray, MRI, PET, …) has been routinely accepted for many years, the development and commercialization of contrast agents designed specifically for ultrasound imaging has occurred only very recently. As in the other imaging modalities, the injection of contrast agents during an ultrasound examination is intended to facilitate the detection and diagnosis of specific pathologies. Contrast agents efficiency is based on the backscattering of ultrasound by microbubbles. These microparticules are intravenously injected in the blood flow. After an introduction and generalities on ultrasound contrast agents (UCA) the microbubble physics in an acoustic field will be developed. Second, physics characteristics of contrast agents will be compared (bubbles with or without shell, gas nature, size distribution). Influence of acoustic pressure on the behaviour of the microparticules (linear, non linear and destruction) will be discussed. Finally, a review of specific imaging adapted to contrast agent properties as harmonic imaging, pulse inversion imaging will be presented.

  20. Solution-based colloidal synthesis of hybrid P3HT: Ternary CuInSe2 nanocomposites using a novel combination of capping agents for low-cost photovoltaics

    NASA Astrophysics Data System (ADS)

    Sharma, Shailesh Narain; Chawla, Parul; Akanksha; Srivastava, A. K.

    2016-06-01

    In this work, ternary CuInSe2 (CISe) chalcopyrite nanocrystallites efficiently passivated by a novel combination of capping agents viz: aniline and 1-octadecene during chemical route synthesis were dispersed in conducting polymer matrix poly(3-hexylthiophene) (P3HT). By varying the composition and concentration of the ligands, the properties of the resulting CISe nanocrystallites and its corresponding polymer nanocomposites thus could be tailored. The structural, morphological and optical studies accomplished by various complimentary techniques viz. Transmission Electron Microscopy (TEM), Contact angle, Photoluminescence (PL) and Raman have enabled us to compare the different hybrid organic (polymer)-inorganic nanocomposites. On the basis of aniline-octadecene equilibrium phase diagram, the polydispersity of the CISe nanocrystals could be tuned by using controlled variations in the reaction conditions of nucleation and growth such as composition of the solvent and temperature. To the best of author's knowledge, the beneficial effects of both the capping agents; aniline and octadecene contributing well in tandem in the development of large-sized (100-125 nm) high quality, sterically- and photo-oxidative stable polycrystalline CISe and its corresponding polymer (P3HT):CISe composites with enhanced charge transfer efficiency has been reported for the first time. The low-cost synthesis and ease of preparation renders this method of great potential for its possible application in low-cost hybrid organic-inorganic photovoltaics. The figure shows the Temperature vs Mole fraction graph of two different phases (aniline and 1-octadecene) in equilibrium.

  1. Facile synthesis of α-Fe{sub 2}O{sub 3}@ porous hollow yeast-based carbonaceous microspheres for fluorescent whitening agent-VBL wastewater treatment

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

    Zheng, Pei; Tong, Zhiqing; Bai, Bo, E-mail: baibochina@163.com

    Porous hollow carbonaceous microspheres (PHCMs) fabricated from yeast cells by hydrothermal treatment have stimulated interest because of their outstanding chemical and physical properties. Herein, the functionalizations of PHCMs by further coating of α-Fe{sub 2}O{sub 3} nanoparticles onto the surface were carried out. The structure of resulted α-Fe{sub 2}O{sub 3}@PHCMs products were characterized by field emission scanning electron microscopy (FE-SEM), energy dispersive spectrometry (EDS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and BET specific surface area measurements (BET), respectively. Its promising application was evaluated by the Fenton-like degradation of fluorescent whitening agent-VBL from aqueous solutions. - Graphical abstract: In thismore » work, novel α-Fe{sub 2}O{sub 3}@porous hollow carbonaceous microspheres (α-Fe{sub 2}O{sub 3}@PHCMs) were synthesized through a combination of hydrothermal method and calcinations route and achieved excellent removal efficiency for fluorescent whitening Agent-VBL. - Highlights: • The hybrid α-Fe{sub 2}O{sub 3}@ porous hollow microspheres (PHCMs) were firstly fabricated. • The formation mechanism of α-Fe{sub 2}O{sub 3}@PHCMs microspheres was proposed and verified. • Dithizone played a key role in the synthesis of α-Fe{sub 2}O{sub 3}@PHCMs composites. • A favorable removal for the fluorescent whitening agent-VBL were achieved.« less

  2. Biologic agents in rheumatology: unmet issues after 200 trials and $200 billion sales.

    PubMed

    Ioannidis, John P A; Karassa, Fotini B; Druyts, Eric; Thorlund, Kristian; Mills, Edward J

    2013-11-01

    Anti-TNF agents and other biologic therapies are widely prescribed for a variety of indications, with total sales that exceed $200 billion to date. In rheumatic diseases, biologic agents have now been studied in more than 200 randomized clinical trials and over 100 subsequent meta-analyses; however, the information obtained does not always meet the needs of patients and clinicians. In this Review, we discuss the current issues concerning the evidence derived from such studies: potential biases favouring positive results; a paucity of head-to-head comparisons between biologically active agents; overwhelming involvement of manufacturer sponsors in trials and in the synthesis of the evidence; the preference for trials with limited follow-up; and the potential for spurious findings on adverse events, leading to endless debates about malignancy risk. We debate the responsibilities of regulatory authorities, the pharmaceutical industry and academia in attempting to solve these shortcomings and challenges. We propose that improvements in the evidence regarding biologic treatments that are continually being added to the therapeutic armamentarium for rheumatic diseases might require revisiting the design and conduct of studies. For example, trials with long-term follow-up that are independent of the pharmaceutical industry, head-to-head comparisons of therapeutic agents and the use of rigorous clinical outcomes should be considered, and public availability of raw data endorsed.

  3. Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents

    DOEpatents

    Katti, Kattesh V.; Gali, Hariprasad; Volkert, Wynn A.

    2004-08-24

    This invention describes a novel strategy to produce phosphine-functionalized biomolecules (e.g. peptides or proteins) for potential use in the design and development of site-specific radiopharmaceuticals for diagnosis or therapy of specific cancers. Hydrophilic alkyl phosphines, in general, tend to be oxidatively unstable. Therefore, incorporation of such phosphine functionalities on peptide (and other biomolecule) backbones, without oxidizing the P.sup.III centers, is difficult. In this context this discovery reports on a new technology by which phosphines, in the form of bifunctional chelating agents, can be directly incorporated on biomolecular backbones using manual synthetic or solid phase peptide synthesis methodologies. The superior ligating abilities of phosphine ligands, with various diagnostically (e.g. TC-99m) or therapeutically (e.g. Re186/188, Rh-105, Au-199) useful radiometals, coupled with the findings that the resulting complexes demonstrate high in vivo stability makes this approach useful in the development of radiolabeled biomolecules for applications in the design of tumor-specific radiopharmaceuticals.

  4. Performance Analysis and Design Synthesis (PADS) computer program. Volume 3: User manual

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The two-fold purpose of the Performance Analysis and Design Synthesis (PADS) computer program is discussed. The program can size launch vehicles in conjunction with calculus-of-variations optimal trajectories and can also be used as a general purpose branched trajectory optimization program. For trajectory optimization alone or with sizing, PADS has two trajectory modules. The first trajectory module uses the method of steepest descent. The second module uses the method of quasi-linearization, which requires a starting solution from the first trajectory module.

  5. Policy design and performance of emissions trading markets: an adaptive agent-based analysis.

    PubMed

    Bing, Zhang; Qinqin, Yu; Jun, Bi

    2010-08-01

    Emissions trading is considered to be a cost-effective environmental economic instrument for pollution control. However, the pilot emissions trading programs in China have failed to bring remarkable success in the campaign for pollution control. The policy design of an emissions trading program is found to have a decisive impact on its performance. In this study, an artificial market for sulfur dioxide (SO2) emissions trading applying the agent-based model was constructed. The performance of the Jiangsu SO2 emissions trading market under different policy design scenario was also examined. Results show that the market efficiency of emissions trading is significantly affected by policy design and existing policies. China's coal-electricity price system is the principal factor influencing the performance of the SO2 emissions trading market. Transaction costs would also reduce market efficiency. In addition, current-level emissions discharge fee/tax and banking mechanisms do not distinctly affect policy performance. Thus, applying emissions trading in emission control in China should consider policy design and interaction with other existing policies.

  6. Design, Synthesis and Bio-evaluation of an EphA2-based Targeted Delivery System

    PubMed Central

    Barile, Elisa; Wang, Si; Das, Swadesh K.; Noberini, Roberta; Dahl, Russell; Stebbins, John L.; Pasquale, Elena B.; Fisher, Paul B.; Pellecchia, Maurizio

    2014-01-01

    We recently described a new targeted delivery system based on specific EphA2 receptor targeting peptides conjugated with the chemotherapeutic agent paclitaxel. In this manuscript we investigate the chemical determinants responsible for the stability and degradation of these agents in plasma. Introducing modifications in both the peptide and the linker between the peptide and paclitaxel, resulted in drug conjugates that are both long-lived in rat plasma and that markedly reduced tumor size in a prostate cancer xenograft model compared to paclitaxel alone treatment. These studies identify critical rate-limiting degradation sites on the peptide-drug conjugates, enabling the design of agents with increased stability and efficacy. These results provide support for our central hypothesis that peptide-drug conjugates targeting the EphA2 receptor represent an innovative and potentially effective strategy to selectively deliver cytotoxic drugs to cancer cells. PMID:24677792

  7. Synthesis and analysis of foam drainage agent for gas well in Jilin Oilfield

    NASA Astrophysics Data System (ADS)

    Qiao, Sanyuan; Liu, Qingwang; Fan, Zhenzhong; Wang, Jigang; Xu, Jianjun

    2017-05-01

    The gas well in Jilin oil field has the characteristics of large temperature variation range and high condensate oil content. So the foam drainage agent of the gas well in Jilin oil field needs to have the performance of oil resistance and less effected by temperature. In this paper, a main foaming agent named lauramidopropyl betaine (LAB) and two kinds of auxiliary foaming agent named sodium alcohol ether sulphate (AES) and lauramidopropylamine oxide (LAO). Through the evaluation of the static foaming capacity and dynamic liquid carrying capacity, the AES is more suitable for LAB. The foaming agent with 70% LAB and 30% AES has 138mm foam height with ROSS-Miles equipment; stirring foam volume can reach 480mL, the half-life of foam is 520s. When the ventilation volume is 8L/min the liquid carrying capacity of 10% of the condensate oil content reached 82g. When the foaming agent concentration is 2%, the liquid carrying capacity of 10% of the condensate oil content reached 75g. When the aeration rate reaches 8-10L/min, the liquid carrying capacity of foam drainage agent can reach the best. The foam drainage agent can retain the performance after 120°C aging for 12h, these performances above can satisfy the requirements for gas well foam drainage in Jilin Oil Field.

  8. Design, Synthesis and Characterisation of New Chimeric Ruthenium(II)-Gold(I) Complexes as Improved Cytotoxic Agents

    PubMed Central

    Massai, Lara; Fernández-Gallardo, Jacob; Guerri, Annalisa; Arcangeli, Annarosa; Pillozzi, Serena

    2015-01-01

    Two heterobimetallic complexes, i.e. [RuCl2(p-cymene)(µ-dppm)AuC] (1) and [RuCl2(p-cymene)(µ-dppm)Au S(thiazoline)] (3), based on known cytotoxic [Ru(p-cymene)Cl2(PR3)] and [AuX(PR3)] (X = Cl, SR) molecular scaffolds, with the diphosphane linker 1,1-bis(diphenylphosphino) methane, dppm, were conveniently prepared and characterised. Remarkably, the new compounds manifested a more favourable in vitro pharmacological profile toward cancer cells than individual ruthenium and gold species being either more cytotoxic or more selective. The interactions of the study compounds with (pBR322) DNA and their inhibitory effects on cathepsin B were also assessed. In addition, their reactivity toward suitable models of protein targets was explored and clear evidence gained for disruption of the bimetallic motif and for protein binding of monometallic fragments. Overall, the data reported here strongly support the concept of multifunctional heterometallic compounds as “improved” candidate agents for cancer treatment. The mechanistic and pharmacological implications of the present findings are discussed. PMID:25996553

  9. Design, synthesis and characterisation of new chimeric ruthenium(II)-gold(I) complexes as improved cytotoxic agents.

    PubMed

    Massai, Lara; Fernández-Gallardo, Jacob; Guerri, Annalisa; Arcangeli, Annarosa; Pillozzi, Serena; Contel, María; Messori, Luigi

    2015-06-28

    Two heterobimetallic complexes, i.e. [RuCl2(p-cymene)(μ-dppm)AuC] (1) and [RuCl2(p-cymene)(μ-dppm)Au(S-thiazoline)] (3), based on known cytotoxic [Ru(p-cymene)Cl2(PR3)] and [AuX(PR3)] (X = Cl, SR) molecular scaffolds, with the diphosphane linker 1,1-bis(diphenylphosphino)methane, dppm, were conveniently prepared and characterised. Remarkably, the new compounds manifested a more favourable in vitro pharmacological profile toward cancer cells than individual ruthenium and gold species being either more cytotoxic or more selective. The interactions of the studied compounds with (pBR322) DNA and their inhibitory effects on cathepsin B were also assessed. In addition, their reactivity toward suitable models of protein targets was explored and clear evidence gained for disruption of the bimetallic motif and for protein binding of monometallic fragments. Overall, the data reported here strongly support the concept of multifunctional heterometallic compounds as "improved" candidate agents for cancer treatment. The mechanistic and pharmacological implications of the present findings are discussed.

  10. Ni-Fe2O4 nanoparticles as contrast agents for magnetic resonance imaging.

    PubMed

    Ahmad, Tanveer; Rhee, Ilsu; Hong, Sungwook; Chang, Yongmin; Lee, Jaejun

    2011-07-01

    Reported herein is the synthesis of a dextran coating on nickel ferrite (Ni-Fe2O4) nanoparticles via chemical coprecipitation. The aqueous solution of the synthesized nanoparticles showed good colloidal stability, and no precipitate was observed 20 months after the synthesis. The coated nanoparticles were found to be cylindrical in shape in the TEM images, and showed a uniform size distribution with an average length and diameter of 17 and 4 nm, respectively. The coated particles were evaluated as potential T1 and T2 contrast agents for MRI. The T1 and T2 relaxations of the hydrogen protons in the water molecules in an aqueous solution of dextran-coated Ni-Fe2O4 nanoparticles were studied. It was found that the T1 relaxivity for the aqueous solution of dextran-coated nanoparticles was slightly greater than that of a commercial Gd-DTPA-BMA contrast agent. The T2 relaxivity, however, was almost twice that of the commercial Gd-DTPA-BMA contrast agent. Animal experimentation also demonstrated that the dextran-coated Ni-Fe2O4 nanoparticles are suitable for use as either T1 or T2 contrast agents in MRI.

  11. Microbial glycolipoprotein-capped silver nanoparticles as emerging antibacterial agents against cholera.

    PubMed

    Gahlawat, Geeta; Shikha, Sristy; Chaddha, Baldev Singh; Chaudhuri, Saumya Ray; Mayilraj, Shanmugam; Choudhury, Anirban Roy

    2016-02-01

    With the increased number of cholera outbreaks and emergence of multidrug resistance in Vibrio cholerae strains it has become necessary for the scientific community to devise and develop novel therapeutic approaches against cholera. Recent studies have indicated plausibility of therapeutic application of metal nano-materials. Among these, silver nanoparticles (AgNPs) have emerged as a potential antimicrobial agent to combat infectious diseases. At present nanoparticles are mostly produced using physical or chemical techniques which are toxic and hazardous. Thus exploitation of microbial systems could be a green eco-friendly approach for the synthesis of nanoparticles having similar or even better antimicrobial activity and biocompatibility. Hence, it would be worth to explore the possibility of utilization of microbial silver nanoparticles and their conjugates as potential novel therapeutic agent against infectious diseases like cholera. The present study attempted utilization of Ochrobactrum rhizosphaerae for the production of AgNPs and focused on investigating their role as antimicrobial agents against cholera. Later the exopolymer, purified from the culture supernatant, was used for the synthesis of spherical shaped AgNPs of around 10 nm size. Further the exopolymer was characterized as glycolipoprotein (GLP). Antibacterial activity of the novel GLP-AgNPs conjugate was evaluated by minimum inhibitory concentration, XTT reduction assay, scanning electron microscopy (SEM) and growth curve analysis. SEM studies revealed that AgNPs treatment resulted in intracellular contents leakage and cell lysis. The potential of microbially synthesized nanoparticles, as novel therapeutic agents, is still relatively less explored. In fact, the present study first time demonstrated that a glycolipoprotein secreted by the O. rhizosphaerae strain can be exploited for production of AgNPs which can further be employed to treat infectious diseases. Although this type of polymer has

  12. Total Synthesis of Jiadifenolide**

    PubMed Central

    Paterson, Ian; Xuan, Mengyang; Dalby, Stephen M

    2014-01-01

    As a potent neurotrophic agent, the sesquiterpenoid jiadifenolide represents a valuable small-molecule lead for the potential therapeutic treatment of neurodegenerative diseases. A stereocontrolled total synthesis of this densely functionalized natural product is reported, central to which is an adventurous samarium-mediated cyclization reaction to establish the tricyclic core and the adjacent C5 and C6 quaternary stereocenters. PMID:24861364

  13. A systematic reactor design approach for the synthesis of active pharmaceutical ingredients.

    PubMed

    Emenike, Victor N; Schenkendorf, René; Krewer, Ulrike

    2018-05-01

    Today's highly competitive pharmaceutical industry is in dire need of an accelerated transition from the drug development phase to the drug production phase. At the heart of this transition are chemical reactors that facilitate the synthesis of active pharmaceutical ingredients (APIs) and whose design can affect subsequent processing steps. Inspired by this challenge, we present a model-based approach for systematic reactor design. The proposed concept is based on the elementary process functions (EPF) methodology to select an optimal reactor configuration from existing state-of-the-art reactor types or can possibly lead to the design of novel reactors. As a conceptual study, this work summarizes the essential steps in adapting the EPF approach to optimal reactor design problems in the field of API syntheses. Practically, the nucleophilic aromatic substitution of 2,4-difluoronitrobenzene was analyzed as a case study of pharmaceutical relevance. Here, a small-scale tubular coil reactor with controlled heating was identified as the optimal set-up reducing the residence time by 33% in comparison to literature values. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Design of a novel class of protein-based magnetic resonance imaging contrast agents for the molecular imaging of cancer biomarkers

    PubMed Central

    Xue, Shenghui; Qiao, Jingjuan; Pu, Fan; Cameron, Mathew; Yang, Jenny J.

    2014-01-01

    Magnetic resonance imaging (MRI) of disease biomarkers, especially cancer biomarkers, could potentially improve our understanding of the disease and drug activity during preclinical and clinical drug treatment and patient stratification. MRI contrast agents with high relaxivity and targeting capability to tumor biomarkers are highly required. Extensive work has been done to develop MRI contrast agents. However, only a few limited literatures report that protein residues can function as ligands to bind Gd3+ with high binding affinity, selectivity, and relaxivity. In this paper, we focus on reporting our current progress on designing a novel class of protein-based Gd3+ MRI contrast agents (ProCAs) equipped with several desirable capabilities for in vivo application of MRI of tumor biomarkers. We will first discuss our strategy for improving the relaxivity by a novel protein-based design. We then discuss the effect of increased relaxivity of ProCAs on improving the detection limits for MRI contrast agent, especially for in vivo application. We will further report our efforts to improve in vivo imaging capability and our achievement in molecular imaging of cancer biomarkers with potential preclinical and clinical applications. PMID:23335551

  15. Solvothermal synthesis of ZnO nanoparticles and anti-infection application in vivo.

    PubMed

    Bai, Xiangyang; Li, Linlin; Liu, Huiyu; Tan, Longfei; Liu, Tianlong; Meng, Xianwei

    2015-01-21

    Zinc oxide nanoparticles (ZnONPs) have been widely studied as the bacteriostatic reagents. However, synthesis of small ZnO nanoparticles with good monodispersion and stability in aqueous solution is still a challenge. Anti-infection research of ZnONPs used as antibacterial agent in vivo is rare. In this paper, a novel, sustainable, and simple method to synthesize ZnO nanoparticles with good monodispersion in aqueous low-temperature conditions and with a small molecule agent is reported. Inhibition zone test and the minimum inhibitory concentration test were performed to examine the antibacterial activity of ZnONPs against bacteria Staphylococcus aureus and Escherichia coli in vitro. For further application in vivo, low cytotoxicity and low acute toxicity in mice of ZnO were demonstrated. Finally, 4 nm ZnONPs combined with poly(vinyl alcohol) gel was used as antibacterial agent in rodent elytritis model, and significant anti-infection effect was proven. In one word, the present research would shed new light on the designing of antibacterial materials like ZnO with promising application in disinfection.

  16. Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review.

    PubMed

    Mousavizadeh, Ali; Jabbari, Ali; Akrami, Mohammad; Bardania, Hassan

    2017-10-01

    Cell targeting peptides (CTP) are small peptides which have high affinity and specificity to a cell or tissue targets. They are typically identified by using phage display and chemical synthetic peptide library methods. CTPs have attracted considerable attention as a new class of ligands to delivery specifically therapeutic and diagnostic agents, because of the fact they have several advantages including easy synthesis, smaller physical sizes, lower immunogenicity and cytotoxicity and their simple and better conjugation to nano-carriers and therapeutic or diagnostic agents compared to conventional antibodies. In this systematic review, we will focus on the basic concepts concerning the use of cell-targeting peptides (CTPs), following the approaches of selecting them from peptide libraries. We discuss several developed strategies for cell-specific delivery of different cargos by CTPs, which are designed for drug delivery and diagnostic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Structure-Based Design: Synthesis, X-ray Crystallography, and Biological Evaluation of N-Substituted-4-Hydroxy-2-Quinolone-3-Carboxamides as Potential Cytotoxic Agents.

    PubMed

    Sabbah, Dima A; Hishmah, Bayan; Sweidan, Kamal; Bardaweel, Sanaa; AlDamen, Murad; Zhong, Haizhen A; Abu Khalaf, Reema; Hasan Ibrahim, Ameerah; Al-Qirim, Tariq; Abu Sheikha, Ghassan; Mubarak, Mohammad S

    2018-01-01

    Oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has been highlighted as a therapeutic target for anticancer drug design. Target compounds were designed to address the effect of different substitution patterns at the N atom of the carboxamide moiety on the bioactivity of this series. Synthesis of the targeted compounds, crystallography, biological evaluation tests against human colon carcinoma (HCT-116), and Glide docking studies. A new series of N-substituted- 4-hydroxy-2-quinolone-3-carboxamides was prepared and characterized by means of FT-IR, 1H and 13C NMR, and elemental analysis. In addition, the identity of the core nucleus 5 was successfully characterized with the aid of X-ray crystallography. Biological activity of prepared compounds was investigated in vitro against human colon carcinoma (HCT-116) cell line. Results revealed that these compounds inhibit cell proliferation and induce apoptosis through an increase in caspase-3 activity and a decrease in DNA cellular content. Compounds 7, 14, and 17 which have H-bond acceptor moiety on p-position displayed promising PI3Kα inhibitory activity. On the other hand, derivatives tailored with bulky and hydrophobic motifs (16 and 18) on o- and m-positions exhibited moderate activity. Molecular docking studies against PI3Kα and caspase-3 showed an agreement between the predicted binding affinity (ΔGobsd) and IC50 values of the derivatives for the caspase-3 model. Furthermore, Glide docking studies against PI3Kα demonstrated that the newly synthesized compounds accommodate PI3Kα kinase catalytic domain and form H-bonding with key binding residues. The series exhibited a potential PI3Kα inhibitory activity in HCT-116 cell line. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Development of a weight/sizing design synthesis computer program. Volume 1: Program formulation

    NASA Technical Reports Server (NTRS)

    Garrison, J. M.

    1973-01-01

    The development of a weight/sizing design synthesis methodology for use in support of the main line space shuttle program is discussed. The methodology has a minimum number of data inputs and quick turn around capabilities. The methodology makes it possible to: (1) make weight comparisons between current shuttle configurations and proposed changes, (2) determine the effects of various subsystems trades on total systems weight, and (3) determine the effects of weight on performance and performance on weight.

  19. Relay tracking control for second-order multi-agent systems with damaged agents.

    PubMed

    Dong, Lijing; Li, Jing; Liu, Qin

    2017-11-01

    This paper investigates a situation where smart agents capable of sensory and mobility are deployed to monitor a designated area. A preset number of agents start tracking when a target intrudes this area. Some of the tracking agents are possible to be out of order over the tracking course. Thus, we propose a cooperative relay tracking strategy to ensure the successful tracking with existence of damaged agents. Relay means that, when a tracking agent quits tracking due to malfunction, one of the near deployed agents replaces it to continue the tracking task. This results in jump of tracking errors and dynamic switching of topology of the multi-agent system. Switched system technique is employed to solve this specific problem. Finally, the effectiveness of proposed tracking strategy and validity of the theoretical results are verified by conducting a numerical simulation. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  20. Deoxypodophyllotoxin: a promising therapeutic agent from herbal medicine.

    PubMed

    Khaled, Meyada; Jiang, Zhen-Zhou; Zhang, Lu-Yong

    2013-08-26

    Recently, biologically active compounds isolated from plants used in herbal medicine have been the center of interest. Deoxypodophyllotoxin (DPT), structurally closely related to the lignan podophyllotoxin, is a potent antitumor and anti-inflammatory agent. However, DPT has not been used clinically yet. Also, DPT from natural sources seems to be unavailable. Hence, it is important to establish alternative resources for the production of such lignan; especially that it is used as a precursor for the semi-synthesis of the cytostatic drugs etoposide phosphate and teniposide. The update paper provides an overview of DPT as an effective anticancer natural compound and a leader for cytotoxic drugs synthesis and development in order to highlight the gaps in our knowledge and explore future research needs. The present review covers the literature available from 1877 to 2012. The information was collected via electronic search using Chinese papers and the major scientific databases including PubMed, Sciencedirect, Web of Science and Google Scholar using the keywords. All abstracts and full-text articles reporting database on the history and current status of DPT were gathered and analyzed. Plants containing DPT have played an important role in traditional medicine. In light of the in vitro pharmacological investigations, DPT is a high valuable medicinal agent that has anti-tumor, anti-proliferative, anti-inflammatory and anti-allergic properties. Further, DPT is an important precursor for the cytotoxic aryltetralin lignan, podophyllotoxin, which is used to obtain semisynthetic derivatives like etoposide and teniposide used in cancer therapy. However, most studies have focused on the in vitro data. Therefore, DPT has not been used clinically yet. DPT has emerged as a potent chemical agent from herbal medicine. Therefore, in vivo studies are needed to carry out clinical trials in humans and enable the development of new anti-cancer agents. In addition, DPT from commercial

  1. Discovery and Development of Natural Product-derived Chemotherapeutic Agents Based on a Medicinal Chemistry Approach⊥†

    PubMed Central

    Lee, Kuo-Hsiung

    2010-01-01

    Medicinal plants have long been an excellent source of pharmaceutical agents. Accordingly, the long term objectives of the author's research program are to discover and design new chemotherapeutic agents based on plant-derived compound leads by using a medicinal chemistry approach, which is a combination of chemistry and biology. Different examples of promising bioactive natural products and their synthetic analogs, including sesquiterpene lactones, quassinoids, naphthoquinones, phenylquinolones, dithiophenediones, neo-tanshinlactone, tylophorine, suksdorfin, DCK, and DCP, will be presented with respect to their discovery and preclinical development as potential clinical trial candidates. Research approaches include bioactivity- or mechanism of action-directed isolation and characterization of active compounds, rational drug design-based modification and analog synthesis, as well as structure-activity relationship and mechanism of action studies. Current clinical trials agents discovered by the Natural Products Research Laboratories, University of North Carolina, include bevirimat (dimethyl succinyl betulinic acid), which is now in Phase IIb trials for treating AIDS. Bevirimat is also the first in a new class of HIV drug candidates called “maturation inhibitors”. In addition, an etoposide analog, GL-331, progressed to anticancer Phase II clinical trials, and the curcumin analog JC-9 is in Phase II clinical trials for treating acne and in development for trials against prostate cancer. The discovery and development of these clinical trials candidates will also be discussed. PMID:20187635

  2. Believable Social and Emotional Agents.

    DTIC Science & Technology

    1996-05-01

    While building tools to support the creation of believable emotional agents, I had to make a number of important design decisions . Before describing...processing systems, it is difficult to give an artist direct control over the emotion - al aspects of the character. By making these decisions explicit, I hope...Woody on “Cheers”). Believable Agents BELIEVABLE SOCIAL AND EMOTIONAL AGENTS 11 Lesson: We don’t want agent architectures that enforce rationality and

  3. Facile Synthesis of Efficient Antibacterial Agent as CoFe₂O₄/Ag Composite Material Against Both Gram-Negative Escherichia coli and Gram-Positive Bacillus subtilis Bacteria.

    PubMed

    Gankhuyag, Sukhbayar; Lee, Kyoung; Bae, Dong Sik

    2018-09-01

    We have suggested that a facile synthesis of CoFe2O4/Ag composite material as an antibacterial agent for substitution of a chlorination agent for microbial infected wastewater treatment. The CoFe2O4/Ag was synthesized by an impregnation method in assistance with trisodium citrate as a reducing agent. The as-prepared uncalcined CoFe2O4 (CFG), calcined CoFe2O4 (CFG600), and calcined CoFe2O4/Ag (CFG600/Ag) composites were characterized by X-ray diffraction (XRD), Field Emission Scanning Electron Microscope (FE-SEM) and Energy Dispersive X-ray (EDX) techniques. Antibacterial activities were also determined in liquid culture by measuring the minimum inhibitory concentrations (MIC) against Gram-negative Escherichia coli (E. coli) and Gram-positive Bacillus subtilis (B. subtilis) bacteria in vitro. Results showed that CFG600/Ag composites had an excellent antibacterial activity in comparison with CFG and CFG600 composites. The CFG600/Ag composites have completely inhibited the growth of both E. coli and B. subtilis bacteria from concentrations of more than 0.25 mg/ml. Furthermore, the FE-SEM study demonstrated the physical damage of bacteria when treated with CFG600/Ag composite material at a concentration of 0.10 mg/ml.

  4. Rational Design and Synthesis of Biologically Active Disubstituted 2(3H) Furanones and Pyrrolone Derivatives as Potent and Safer Non Steroidal Anti-inflammatory Agents.

    PubMed

    Khokra, S L; Khan, S A; Choudhary, D; Hasan, S M; Ahmad, A; Husain, Asif

    2016-01-01

    Furanone and pyrrolone heterocyclic ring system represent important and interesting classes of bioactive compounds. Medicinal chemists use these heterocycyclic moieties as scaffolds in drug design and discovery. A series of 3-arylidene-5-(naphthalene-2-yl)-furan-2(3H)-ones (2a-j) were synthesized by incorporating pharmacophore of COX-2 inhibitor rofecoxib and naphthyl ring of naproxen as potential non steroidal anti-inflammatory agents. These furanone derivatives were subsequently reacted with dry ammonia gas and benzylamine to furnish corresponding 3-arylidene-5-(naphthlen-2-yl)-1H-pyrrol-2(3H)-ones (3a-e) and 3-arylidene-1-benzyl-5- (naphthalene-2-yl)-1H-pyrrol-2(3H)-ones (4a-e), respectively. The newly prepared heterocyclics were screened for their expected in-vivo biological activities including anti-inflammatory, analgesic and ulcerogenic actions in rodents. The COX-2 inhibitory behavior of synthesized compounds was also assessed via automated docking studies. The chemical structure of the synthesized compounds was characterized by using modern spectroscopic techniques. Result of in-vivo pharmacological studies demonstrated that almost all N-Benzyl-pyrrol-2(3H)-ones (4a-e) showed better anti-inflammatory and analgesic activities in comparison with the other two series of furan-2(3H)-ones and pyrrol- 2(3H)-ones. The moldock score value of the tested compounds was found in the range of -116.66 to -170.328 and was better than the standard drug. Among all the synthesized compounds, only nine compounds (2d, 2g, 2h, 3d, 4a, 4b, 4c, 4d and 4e) exhibited potent anti-inflammatory and analgesic activities with significantly reduced gastrointestinal toxicity in various animal models in comparison to standard drug, diclofenac. Therefore, it is recommended to explore the potential of the synthesized compounds as lead candidates for the development of new therapeutic agents.

  5. Triblock copolymer-mediated synthesis of catalytically active gold nanostructures

    NASA Astrophysics Data System (ADS)

    Santos, Douglas C.; de Souza, Viviane C.; Vasconcelos, Diego A.; Andrade, George R. S.; Gimenez, Iara F.; Teixeira, Zaine

    2018-04-01

    The design of nanostructures based on poly(ethylene oxide)-poly(propylene)-poly(ethylene oxide) (PEO-PPO-PEO) and metal nanoparticles is becoming an important research topic due to their multiple functionalities in different fields, including nanomedicine and catalysis. In this work, water-soluble gold nanoparticles have been prepared through a green aqueous synthesis method using Pluronic F127 as both reducing and stabilizing agents. The size dependence (varying from 2 to 70 nm) and stability of gold nanoparticles were systematically studied by varying some parameters of synthesis, which were the polymer concentration, temperature, and exposure to UV-A light, being monitored by UV-Vis spectroscopy and TEM. Also, an elaborated study regarding to the kinetic of formation (nucleation and growth) was presented. Finally, the as-prepared Pluronic-capped gold nanoparticles have shown excellent catalytic activity towards the reduction of 4-nitrophenol to 4-aminophenol with sodium borohydride, in which a higher catalytic performance was exhibited when compared with gold nanoparticles prepared by classical reduction method using sodium citrate. [Figure not available: see fulltext.

  6. Eco-friendly green synthesis of silver nanoparticles using salmalia malabarica: synthesis, characterization, antimicrobial, and catalytic activity studies

    NASA Astrophysics Data System (ADS)

    Murali Krishna, I.; Bhagavanth Reddy, G.; Veerabhadram, G.; Madhusudhan, A.

    2016-06-01

    An economically viable and "green" process has been developed for the synthesis of silver nanoparticles (AgNPs) with an average size of 7 nm using non-toxic and renewable salmalia malabarica gum (SMG) as reducing and capping agent without using any chemical reducing agent. The effect of various parameters such as concentration of SMG and silver nitrate and reaction time for the synthesis of AgNPs was studied. The synthesized AgNPs are systematically characterized by UV/Vis spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction and Transmission electron microscopy. The resultant SMG-capped AgNPs are highly stable and had significant antibacterial action on both Escherichia coli ( E. coli) and Staphylococcus aureus ( S. aureus). The catalytic action of the SMG-capped AgNPs to initiate the reduction of 4-nitrophenol (4-NP) in the presence of NaBH4 has also been reported. The kinetics of the reaction was found to be of pseudo-first-order with respect to the 4-NP.

  7. Biodirected synthesis of Miconazole-conjugated bacterial silver nanoparticles and their application as antifungal agents and drug delivery vehicles.

    PubMed

    Kumar, C Ganesh; Poornachandra, Y

    2015-01-01

    The recent strategy to improve the efficacy of drugs is to combine them with metal nanoparticles for the control of microbial infections. Considering this fact, we developed a low cost and eco-friendly method for silver nanoparticles synthesis using the cell free supernatant of Delftia sp. strain KCM-006 and their application as antifungal agents and as a drug carrier. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis revealed the formation of spherical and monodispersed silver nanoparticles with an average size of 9.8 nm. The synthesized nanoparticles were found to be photoluminescent, highly stable and crystalline in nature having a zeta potential of -31 mV. The silver nanoparticles exhibited very good antifungal activity against various pathogenic Candida strains. Furthermore, the efficacy of nanoparticles was increased by conjugating the antifungal drug Miconazole to silver nanoparticles which exhibited significant fungicidal activity, inhibition of ergosterol biosynthesis and biofilm inhibition by increasing ROS levels. In addition, the cell viability and immunocytochemistry analysis against different normal cell lines including Chinese hamster ovary cells (CHO), human lung cell line (MRC5) and human vascular endothelial cells (HUVEC) demonstrated that these nanoparticles were non-toxic up to a concentration of 20 μM. In conclusion, these results suggest that the synthesized nanoparticles find application as both antifungal agents and drug delivery vehicles. This is a first report on the preparation of silver nanoparticles using culture supernatant from Delftia sp. and also on the conjugation of Miconazole, an antifungal drug, to the bacterial silver nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Design and Analysis of Cost-Efficient Sensor Deployment for Tracking Small UAS with Agent-Based Modeling.

    PubMed

    Shin, Sangmi; Park, Seongha; Kim, Yongho; Matson, Eric T

    2016-04-22

    Recently, commercial unmanned aerial systems (UAS) have gained popularity. However, these UAS are potential threats to people in terms of safety in public places, such as public parks or stadiums. To reduce such threats, we consider a design, modeling, and evaluation of a cost-efficient sensor system that detects and tracks small UAS. In this research, we focus on discovering the best sensor deployments by simulating different types and numbers of sensors in a designated area, which provide reasonable detection rates at low costs. Also, the system should cover the crowded areas more thoroughly than vacant areas to reduce direct threats to people underneath. This research study utilized the Agent-Based Modeling (ABM) technique to model a system consisting of independent and heterogeneous agents that interact with each other. Our previous work presented the ability to apply ABM to analyze the sensor configurations with two types of radars in terms of cost-efficiency. The results from the ABM simulation provide a list of candidate configurations and deployments that can be referred to for applications in the real world environment.

  9. Design and Analysis of Cost-Efficient Sensor Deployment for Tracking Small UAS with Agent-Based Modeling

    PubMed Central

    Shin, Sangmi; Park, Seongha; Kim, Yongho; Matson, Eric T.

    2016-01-01

    Recently, commercial unmanned aerial systems (UAS) have gained popularity. However, these UAS are potential threats to people in terms of safety in public places, such as public parks or stadiums. To reduce such threats, we consider a design, modeling, and evaluation of a cost-efficient sensor system that detects and tracks small UAS. In this research, we focus on discovering the best sensor deployments by simulating different types and numbers of sensors in a designated area, which provide reasonable detection rates at low costs. Also, the system should cover the crowded areas more thoroughly than vacant areas to reduce direct threats to people underneath. This research study utilized the Agent-Based Modeling (ABM) technique to model a system consisting of independent and heterogeneous agents that interact with each other. Our previous work presented the ability to apply ABM to analyze the sensor configurations with two types of radars in terms of cost-efficiency. The results from the ABM simulation provide a list of candidate configurations and deployments that can be referred to for applications in the real world environment. PMID:27110790

  10. Converting a Natural Protein Compartment into a Nanofactory for the Size-Constrained Synthesis of Antimicrobial Silver Nanoparticles.

    PubMed

    Giessen, Tobias W; Silver, Pamela A

    2016-12-16

    Engineered biological systems are used extensively for the production of high value and commodity organics. On the other hand, most inorganic nanomaterials are still synthesized via chemical routes. By engineering cellular compartments, functional nanoarchitectures can be produced under environmentally sustainable conditions. Encapsulins are a new class of microbial nanocompartments with promising applications in nanobiotechnology. Here, we engineer the Thermotoga maritima encapsulin EncTm to yield a designed compartment for the size-constrained synthesis of silver nanoparticles (Ag NPs). These Ag NPs exhibit uniform shape and size distributions as well as long-term stability. Ambient aqueous conditions can be used for Ag NP synthesis, while no reducing agents or solvents need to be added. The antimicrobial activity of the synthesized protein-coated or shell-free Ag NPs is superior to that of silver nitrate and citrate-capped Ag NPs. This study establishes encapsulins as an engineerable platform for the synthesis of biogenic functional nanomaterials.

  11. Design, Synthesis and Evaluation of Novel 2,5,6-Trisubstituted Benzimidazoles Targeting FtsZ as Antitubercular Agents

    PubMed Central

    Park, Bora; Awasthi, Divya; Chowdhury, Soumya R.; Melief, Eduard H.; Kumar, Kunal; Knudson, Susan E.; Slayden, Richard A.; Ojima, Iwao

    2014-01-01

    Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 μg/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63–12.5 μg/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to be 1.32 μM. PMID:24726304

  12. Agent oriented programming

    NASA Technical Reports Server (NTRS)

    Shoham, Yoav

    1994-01-01

    The goal of our research is a methodology for creating robust software in distributed and dynamic environments. The approach taken is to endow software objects with explicit information about one another, to have them interact through a commitment mechanism, and to equip them with a speech-acty communication language. System-level applications include software interoperation and compositionality. A government application of specific interest is an infrastructure for coordination among multiple planners. Daily activity applications include personal software assistants, such as programmable email, scheduling, and new group agents. Research topics include definition of mental state of agents, design of agent languages as well as interpreters for those languages, and mechanisms for coordination within agent societies such as artificial social laws and conventions.

  13. Synthesis of Pharmacological Heterocyclic Derivatives Based Surfactants.

    PubMed

    El-Sayed, Refat; Fadda, Ahmed A

    2016-01-01

    Synthesis of chromenopyrimidine derivatives and the related fused system carried out by the reaction of chromene derivative 1 with various reagents under suitable reaction conditions. Condensation of stearoyl chloride with these heterocycles, then, propoxylated the products using propylene oxide to produce surface active agents having a twofold capacity as surface and antimicrobial dynamic specialists which may be served in the production of medications, pesticides, beautifying agents or may be utilized as an antimicrobial. Some of the surface properties and antimicrobial activity were resolved.

  14. Synthesis and evaluation of new 3-phenylcoumarin derivatives as potential antidepressant agents.

    PubMed

    Sashidhara, Koneni V; Rao, K Bhaskara; Singh, Seema; Modukuri, Ram K; Aruna Teja, G; Chandasana, Hardik; Shukla, Shubha; Bhatta, Rabi S

    2014-10-15

    A series of amine substituted 3-phenyl coumarin derivatives were designed and synthesized as potential antidepressant agents. In preliminary screening, all compounds were evaluated in forced swimming test (FST), a model to screen antidepressant activity in rodents. Among the series, compounds 5c and 6a potentially decreased the immobility time by 73.4% and 79.7% at a low dose of 0.5 mg/kg as compared to standard drug fluoxetine (FXT) which reduced the immobility time by 74% at a dose of 20 mg/kg, ip. Additionally, these active compounds also exhibited significant efficacy in tail suspension test (TST) (another model to screen antidepressant compounds). Interestingly, rotarod and locomotor activity tests confirmed that these two compounds do not have any motor impairment effect and neurotoxicity in mice. Our studies demonstrate that the new 3-phenylcoumarin derivatives may serve as a promising antidepressant lead and hence pave the way for further investigation around this chemical space. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. New Paradigm Shift for the Green Synthesis of Antibacterial Silver Nanoparticles Utilizing Plant Extracts

    PubMed Central

    2014-01-01

    This review covers general information regarding the green synthesis of antibacterial silver nanoparticles. Owing to their antibacterial properties, silver nanoparticles are widely used in many areas, especially biomedical applications. In green synthesis practices, the chemical reducing agents are eliminated, and biological entities are utilized to convert silver ions to silver nanoparticles. Among the various biological entities, natural plant extracts have emerged as green reducing agents, providing eco-friendly routes for the preparation of silver nanomaterials. The most obvious merits of green synthesis are the increased biocompatibility of the resulting silver nanoparticles and the ease with which the reaction can be carried out. This review summarizes some of the plant extracts that are used to produce antibacterial silver nanoparticles. Additionally, background information regarding the green synthesis and antibacterial activity of silver nanoparticles is provided. Finally, the toxicological aspects of silver nanoparticles are briefly mentioned. PMID:25343010

  16. Design and chemical synthesis of iodine-containing molecules for application to solar-pumped I* lasers

    NASA Technical Reports Server (NTRS)

    Shiner, Christopher S.

    1986-01-01

    Research is directed toward the design and synthesis of new media for solar-pumped I* lasers. Since the most effective existing lasants are perfluoroalkyl iodides, a strategy was proposed for the development of improved materials of this type with absorption maxima at 300 nm. Absorption spectra were synthesized and measured for prototypical species containing iodine bound to boron, iron, and cobalt.

  17. 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.

  18. The Design of a Polymorphous Cognitive Agent Architecture (PCAA)

    DTIC Science & Technology

    2008-05-01

    tree, and search agents may search the tree for documents or clusters, depositing pheromones on the way down the tree. 46 19 The quality of SODAS...location in the lattice is a node, connected to its neighbors by links, and agents roam across the lattice, depositing pheromones . 49 21 A possible FPGA...provided by swarming, and also figure out a way for learning in ACT-R to trickle down to swarming computations, e.g., through the pheromones . Integration

  19. Synthesis and Characterization of Fe3O4 Nanoparticles using Polyvinyl Alcohol (PVA) as Capping Agent and Glutaraldehyde (GA) as Crosslinker

    NASA Astrophysics Data System (ADS)

    Budi Hutami Rahayu, Lale; Oktavia Wulandari, Ika; Herry Santjojo, Djoko; Sabarudin, Akhmad

    2018-01-01

    The use of polyvinyl alcohol (PVA) as a capping agent and glutaraldehyde (GA) as a crosslinker for a synthesis of magnetite (Fe3O4) nanoparticles is able to reduce agglomeration of produced Fe3O4. Additionally, oxidation of Fe3O4 by air could be avoided. The synthesis is carried out in two steps: first step, magnetite (Fe3O4) nanoparticles were prepared by dissolving the FeCl3.6H2O and FeCl2.4H2O in alkaline media (NH3.H2O). The second step, magnetite nanoparticles were coated with polyvinyl alcohol (PVA) and glutaraldehyde (GA) to obtain Fe3O4-PVA-GA. The latter material was then characterized by FTIR to determine the typical functional groups of magnetite coated with PVA-GA. X-ray Diffraction analysis was used to determine structure and size of crystal as well as the percentage of magnetite produced. It was found that the produced nanoparticles have crystal sizes around 4-9 nm with the cubic crystal structure. The percentage of magnetite phase increases when the amount of glutaraldehyde increased. SEM-EDX was employed to assess the surface morphology and elemental composition of the resulted nanoparticles. The magnetic character of the magnetite and Fe3O4- PVA-GA were studied using Electron Spin Resonance.

  20. Ambient agents: embedded agents for remote control and monitoring using the PANGEA platform.

    PubMed

    Villarrubia, Gabriel; De Paz, Juan F; Bajo, Javier; Corchado, Juan M

    2014-07-31

    Ambient intelligence has advanced significantly during the last few years. The incorporation of image processing and artificial intelligence techniques have opened the possibility for such aspects as pattern recognition, thus allowing for a better adaptation of these systems. This study presents a new model of an embedded agent especially designed to be implemented in sensing devices with resource constraints. This new model of an agent is integrated within the PANGEA (Platform for the Automatic Construction of Organiztions of Intelligent Agents) platform, an organizational-based platform, defining a new sensor role in the system and aimed at providing contextual information and interacting with the environment. A case study was developed over the PANGEA platform and designed using different agents and sensors responsible for providing user support at home in the event of incidents or emergencies. The system presented in the case study incorporates agents in Arduino hardware devices with recognition modules and illuminated bands; it also incorporates IP cameras programmed for automatic tracking, which can connect remotely in the event of emergencies. The user wears a bracelet, which contains a simple vibration sensor that can receive notifications about the emergency situation.

  1. Ambient Agents: Embedded Agents for Remote Control and Monitoring Using the PANGEA Platform

    PubMed Central

    Villarrubia, Gabriel; De Paz, Juan F.; Bajo, Javier; Corchado, Juan M.

    2014-01-01

    Ambient intelligence has advanced significantly during the last few years. The incorporation of image processing and artificial intelligence techniques have opened the possibility for such aspects as pattern recognition, thus allowing for a better adaptation of these systems. This study presents a new model of an embedded agent especially designed to be implemented in sensing devices with resource constraints. This new model of an agent is integrated within the PANGEA (Platform for the Automatic Construction of Organiztions of Intelligent Agents) platform, an organizational-based platform, defining a new sensor role in the system and aimed at providing contextual information and interacting with the environment. A case study was developed over the PANGEA platform and designed using different agents and sensors responsible for providing user support at home in the event of incidents or emergencies. The system presented in the case study incorporates agents in Arduino hardware devices with recognition modules and illuminated bands; it also incorporates IP cameras programmed for automatic tracking, which can connect remotely in the event of emergencies. The user wears a bracelet, which contains a simple vibration sensor that can receive notifications about the emergency situation. PMID:25090416

  2. Chemical synthesis, NMR analysis and evaluation on a cancer xenograft model (HL-60) of the aminosteroid derivative RM-133.

    PubMed

    Maltais, René; Hospital, Audrey; Delhomme, Audrey; Roy, Jenny; Poirier, Donald

    2014-04-01

    The aminosteroid derivative RM-133 has been reported to be a promising pro-apoptotic agent showing activity on various cancer cell lines. Following the development of solid-phase synthesis that generated a series of libraries of aminosteroid derivatives, we now report the development of a convenient liquid phase chemical synthesis of RM-133, the most promising candidate, in order to obtain sufficient quantities to proceed with the first preclinical assays. A simple and convergent six-step synthesis was designed and allowed the preparation of a gram-quantity scale of RM-133. This aminosteroid derivative was also fully characterized by NMR experiments which revealed an interesting mixture of conformers. Finally, the in vivo potency of RM-133 was evaluated on a xenograft model in nude mice with HL-60 tumors, which has resulted in the blocking of tumor progression by 57%. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Interdisciplinary Learning for Chemical Engineering Students from Organic Chemistry Synthesis Lab to Reactor Design to Separation

    ERIC Educational Resources Information Center

    Armstrong, Matt; Comitz, Richard L.; Biaglow, Andrew; Lachance, Russ; Sloop, Joseph

    2008-01-01

    A novel approach to the Chemical Engineering curriculum sequence of courses at West Point enabled our students to experience a much more realistic design process, which more closely replicated a real world scenario. Students conduct the synthesis in the organic chemistry lab, then conduct computer modeling of the reaction with ChemCad and…

  4. ADS: A FORTRAN program for automated design synthesis: Version 1.10

    NASA Technical Reports Server (NTRS)

    Vanderplaats, G. N.

    1985-01-01

    A new general-purpose optimization program for engineering design is described. ADS (Automated Design Synthesis - Version 1.10) is a FORTRAN program for solution of nonlinear constrained optimization problems. The program is segmented into three levels: strategy, optimizer, and one-dimensional search. At each level, several options are available so that a total of over 100 possible combinations can be created. Examples of available strategies are sequential unconstrained minimization, the Augmented Lagrange Multiplier method, and Sequential Linear Programming. Available optimizers include variable metric methods and the Method of Feasible Directions as examples, and one-dimensional search options include polynomial interpolation and the Golden Section method as examples. Emphasis is placed on ease of use of the program. All information is transferred via a single parameter list. Default values are provided for all internal program parameters such as convergence criteria, and the user is given a simple means to over-ride these, if desired.

  5. Microbial synthesis of poly(epsilon-lysine) and its various applications.

    PubMed

    Shih, Ing-Lung; Shen, Ming-Haw; Van, Yi-Tsong

    2006-06-01

    This review article deals with the microbial synthesis, physiochemical properties, and potential applications of poly-epsilon-lysine (epsilon-PL), which is a naturally occurring biomaterial that is water soluble, biodegradable, edible and non-toxic toward humans and the environment. The potential applications of epsilon-PL as food preservatives, emulsifying agent, dietary agent, biodegradable fibers, highly water absorbable hydrogels, drug carriers, anticancer agent enhancer, biochip coatings in the fields of food, medicine, agriculture and electronics are also discussed in this review.

  6. Simple sol-gel synthesis and characterization of new CoTiO3/CoFe2O4 nanocomposite by using liquid glucose, maltose and starch as fuel, capping and reducing agents.

    PubMed

    Ansari, Fatemeh; Sobhani, Azam; Salavati-Niasari, Masoud

    2018-03-15

    The sol-gel auto-combustion technique is an effective method for the synthesis of the composites. In this research for the first time, CoTiO 3 /CoFe 2 O 4 nanocomposites are successfully synthesized via a new sol-gel auto-combustion technique. The glucose, maltose and starch are used as fuel, capping and reducing agents, also the optimal reducing agent is chosen. The effects of quantity of reducing agent, molar ratio of Ti:Co, calcination temperature and time on the morphology, particle size, magnetic property, purity and phase of the nanocomposites are investigated. XRD patterns show formation of CoTiO 3 /CoFe 2 O 4 spherical nanoparticles with nearly evenly distribution, when the molar ratio of Co/Ti is 1:1. EDS analysis confirm results of XRD. The magnetic behavior of the nanocomposites is studied by VSM. The nanocomposites exhibit a high coercivity at room temperature. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Design of a Mobile Agent-Based Adaptive Communication Middleware for Federations of Critical Infrastructure Simulations

    NASA Astrophysics Data System (ADS)

    Görbil, Gökçe; Gelenbe, Erol

    The simulation of critical infrastructures (CI) can involve the use of diverse domain specific simulators that run on geographically distant sites. These diverse simulators must then be coordinated to run concurrently in order to evaluate the performance of critical infrastructures which influence each other, especially in emergency or resource-critical situations. We therefore describe the design of an adaptive communication middleware that provides reliable and real-time one-to-one and group communications for federations of CI simulators over a wide-area network (WAN). The proposed middleware is composed of mobile agent-based peer-to-peer (P2P) overlays, called virtual networks (VNets), to enable resilient, adaptive and real-time communications over unreliable and dynamic physical networks (PNets). The autonomous software agents comprising the communication middleware monitor their performance and the underlying PNet, and dynamically adapt the P2P overlay and migrate over the PNet in order to optimize communications according to the requirements of the federation and the current conditions of the PNet. Reliable communications is provided via redundancy within the communication middleware and intelligent migration of agents over the PNet. The proposed middleware integrates security methods in order to protect the communication infrastructure against attacks and provide privacy and anonymity to the participants of the federation. Experiments with an initial version of the communication middleware over a real-life networking testbed show that promising improvements can be obtained for unicast and group communications via the agent migration capability of our middleware.

  8. Facile synthesis and biological evaluation of novel symmetrical biphenyls as antitumor agents.

    PubMed

    Zhang, Jie; Zhang, Yanmin; Pan, Xiaoyan; Wang, Chen; Hu, Zhigang; Wang, Sicen; He, Langchong

    2012-03-01

    As a continuation to our previous work in developing anticancer agents, eighteen symmetrical biphenyl derivatives structurally related to taspine were synthesized and evaluated in vitro and in vivo. All the compounds were prepared with varied substitutions in the phenyl ring of aniline moiety. The cytotoxicity and anticancer activity of biphenyls was evaluated against various human tumor and normal cell line. Antiproliferative assays indicated that some of them exhibited potent anticancer activity. The potent antiproliferative activity of these compounds against ECV304 suggested that these biphenyls could be served as antiangiogenic agents. The highly active compound (2) also exhibited potent growth inhibition against cancer cell lines in vivo. Our findings demonstrated that these symmetrical biphenyl derivatives would be a promising candidate as novel anticancer agents.

  9. Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents.

    PubMed

    Park, Bora; Awasthi, Divya; Chowdhury, Soumya R; Melief, Eduard H; Kumar, Kunal; Knudson, Susan E; Slayden, Richard A; Ojima, Iwao

    2014-05-01

    Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 μg/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63-12.5 μg/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to be 1.32 μM. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Synthesis and characterization of hydrogen-bond acidic functionalized graphene

    NASA Astrophysics Data System (ADS)

    Yang, Liu; Han, Qiang; Pan, Yong; Cao, Shuya; Ding, Mingyu

    2014-05-01

    Hexafluoroisopropanol phenyl group functionalized materials have great potential in the application of gas-sensitive materials for nerve agent detection, due to the formation of strong hydrogen-bonding interactions between the group and the analytes. In this paper, take full advantage of ultra-large specific surface area and plenty of carbon-carbon double bonds and hexafluoroisopropanol phenyl functionalized graphene was synthesized through in situ diazonium reaction between -C=C- and p-hexafluoroisopropanol aniline. The identity of the as-synthesis material was confirmed by transmission electron microscopy, Raman spectroscopy, ultraviolet visible spectroscopy, X-ray photoelectron spectroscopy and thermo gravimetric analysis. The synthesis method is simply which retained the excellent physical properties of original graphene. In addition, the novel material can be assigned as an potential candidate for gas sensitive materials towards organophosphorus nerve agent detection.

  11. Luminescent Porous Polymers Based on Aggregation-Induced Mechanism: Design, Synthesis and Functions.

    PubMed

    Dalapati, Sasanka; Gu, Cheng; Jiang, Donglin

    2016-12-01

    Enormous research efforts are focusing on the design and synthesis of advanced luminescent systems, owing to their diverse capability in scientific studies and technological developments. In particular, fluorescence systems based on aggregation-induced emission (AIE) have emerged to show great potential for sensing, bio-imaging, and optoelectronic applications. Among them, integrating AIE mechanisms to design porous polymers is unique because it enables the combination of porosity and luminescence activity in one molecular skeleton for functional design. In recent years rapid progress in exploring AIE-based porous polymers has developed a new class of luminescent materials that exhibit broad structural diversity, outstanding properties and functions and promising applications. By classifying the structural nature of the skeleton, herein the design principle, synthetic development and structural features of different porous luminescent materials are elucidated, including crystalline covalent organic frameworks (COFs), metal-organic frameworks (MOFs), and amorphous porous organic polymers (POPs). The functional exploration of these luminescent porous polymers are highlighted by emphasizing electronic interplay within the confined nanospace, fundamental issues to be addressed are disclosed, and future directions from chemistry, physics and materials science perspectives are proposed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Design, Synthesis and Evaluation of 2,5-Diketopiperazines as Inhibitors of the MDM2-p53 Interaction.

    PubMed

    Pettersson, Mariell; Quant, Maria; Min, Jaeki; Iconaru, Luigi; Kriwacki, Richard W; Waddell, M Brett; Guy, R Kiplin; Luthman, Kristina; Grøtli, Morten

    2015-01-01

    The transcription factor p53 is the main tumour suppressor in cells and many cancer types have p53 mutations resulting in a loss of its function. In tumours that retain wild-type p53 function, p53 activity is down-regulated by MDM2 (human murine double minute 2) via a direct protein-protein interaction. We have designed and synthesised two series of 2,5-diketopiperazines as inhibitors of the MDM2-p53 interaction. The first set was designed to directly mimic the α-helical region of the p53 peptide, containing key residues in the i, i+4 and i+7 positions of a natural α-helix. Conformational analysis indicated that 1,3,6-trisubstituted 2,5-diketopiperazines were able to place substituents in the same spatial orientation as an α-helix template. The key step of the synthesis involved the cyclisation of substituted dipeptides. The other set of tetrasubstituted 2,5-diketopiperazines were designed based on structure-based docking studies and the Ugi multicomponent reaction was used for the synthesis. This latter set comprised the most potent inhibitors which displayed micromolar IC50-values in a biochemical fluorescence polarisation assay.

  13. Design, Synthesis and Evaluation of 2,5-Diketopiperazines as Inhibitors of the MDM2-p53 Interaction

    PubMed Central

    Pettersson, Mariell; Quant, Maria; Min, Jaeki; Iconaru, Luigi; Kriwacki, Richard W.; Waddell, M. Brett; Guy, R. Kiplin; Luthman, Kristina; Grøtli, Morten

    2015-01-01

    The transcription factor p53 is the main tumour suppressor in cells and many cancer types have p53 mutations resulting in a loss of its function. In tumours that retain wild-type p53 function, p53 activity is down-regulated by MDM2 (human murine double minute 2) via a direct protein—protein interaction. We have designed and synthesised two series of 2,5-diketopiperazines as inhibitors of the MDM2-p53 interaction. The first set was designed to directly mimic the α-helical region of the p53 peptide, containing key residues in the i, i+4 and i+7 positions of a natural α-helix. Conformational analysis indicated that 1,3,6-trisubstituted 2,5-diketopiperazines were able to place substituents in the same spatial orientation as an α-helix template. The key step of the synthesis involved the cyclisation of substituted dipeptides. The other set of tetrasubstituted 2,5-diketopiperazines were designed based on structure-based docking studies and the Ugi multicomponent reaction was used for the synthesis. This latter set comprised the most potent inhibitors which displayed micromolar IC50-values in a biochemical fluorescence polarisation assay. PMID:26427060

  14. Nondestructive Intervention to Multi-Agent Systems through an Intelligent Agent

    PubMed Central

    Han, Jing; Wang, Lin

    2013-01-01

    For a given multi-agent system where the local interaction rule of the existing agents can not be re-designed, one way to intervene the collective behavior of the system is to add one or a few special agents into the group which are still treated as normal agents by the existing ones. We study how to lead a Vicsek-like flocking model to reach synchronization by adding special agents. A popular method is to add some simple leaders (fixed-headings agents). However, we add one intelligent agent, called ‘shill’, which uses online feedback information of the group to decide the shill's moving direction at each step. A novel strategy for the shill to coordinate the group is proposed. It is strictly proved that a shill with this strategy and a limited speed can synchronize every agent in the group. The computer simulations show the effectiveness of this strategy in different scenarios, including different group sizes, shill speed, and with or without noise. Compared to the method of adding some fixed-heading leaders, our method can guarantee synchronization for any initial configuration in the deterministic scenario and improve the synchronization level significantly in low density groups, or model with noise. This suggests the advantage and power of feedback information in intervention of collective behavior. PMID:23658695

  15. Design, Synthesis and Biological Evaluation of4-(Imidazolylmethyl)-2-(4-methylsulfonyl phenyl)-Quinoline Derivatives as Selective COX-2 Inhibitors and In-vitro Anti-breast Cancer Agents

    PubMed Central

    Ghodsi, Razieh; Azizi, Ebrahim; Zarghi, Afshin

    2016-01-01

    A new group of 4-(Imidazolylmethyl)quinoline derivatives possessing a methylsulfonyl COX-2 pharmacophore at the para position of the C-2 phenyl ring were designed and synthesized as selective COX-2 inhibitors and in-vitroanti breast cancer agents. In-vitro COX-1 and COX-2 inhibition studies showed that all the compounds were potent and selective inhibitors of the COX-2 isozyme with IC50 values in the potent range 0.063-0.090 µM, and COX-2 selectivity indexes in the 179.9 to 547.6 range. Molecular modeling studies indicated that the methylsulfonyl substituent can be inserted into the secondary pocket of COX-2 active site for interactions with Arg513. Cytotoxicity of quinolines 9a-e against human breast cancer MCF-7 and T47D cell lines were also evaluated. All the compounds 9a-e were more cytotoxic against MCF-7 cells in comparison with those of T47D which express aromatase mRNA less than MCF-7 cells.The data showed that the increase of lipophilic properties of substituents on the C-7 and C-8 quinoline ring increased their cytotoxicity on MCF-7cells andCOX-2 inhibitory activity. Among the quinolines 9a-e, 4-((1H-Imidazol-1-yl)methyl) 7,8,9,10-tetrahydro-2-(4-methylsulfonylphenyl)-benzo[h]quinoline (9d)was identified as the most potent andselective COX-2inhibitor as well as the most cytotoxic agent against MCF-7 cells. PMID:27610157

  16. Ultrasound-accelerated synthesis of biphenyl compounds using novel Pd(0) nanoparticles immobilized on bio-composite.

    PubMed

    Baran, Talat

    2018-07-01

    This study describes (i) an eco-friendly approach for design of Pd(0) nanoparticles on a natural composite, which is composed of carboxymethyl cellulose/agar polysaccharides (CMC/AG), without using any toxic reducing agents and (ii) development of ultrasound assisted simple protocol for synthesis of biphenyl compounds. Chemical characterization studies of Pd(0) nanoparticles (Pd NPs@CMC/AG) revealed that size of the particles were in the range of 37-55 nm. Catalytic performance of Pd NPs@CMC/AG was evaluated in synthesis of various biphenyl compounds by using the ultrasound-assisted method that was developed in this study. Pd NPs@CMC/AG exhibited excellent catalytic performance by producing high reaction yields. In addition, Pd NPs@CMC/AG was successfully used up to six reaction cycles without losing its catalytic activity, indicating high reproducibility of Pd NPs@CMC/AG. Additionally, compared to conventional the methods, new ultrasound-assisted synthesis technique that was followed in this study exhibited some advantages such as shorter reaction time, greener reaction conditions, higher yields and easier work-up. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Harnessing Intracellular Biochemical Pathways for In Vitro Synthesis of Designer Tellurium Nanorods.

    PubMed

    Xiong, Ling-Hong; Cui, Ran; Zhang, Zhi-Ling; Tu, Jia-Wei; Shi, Yun-Bo; Pang, Dai-Wen

    2015-10-28

    Synthesizing nanomaterials of desired properties is a big challenge, which requires extremely harsh conditions and/or use of toxic materials. More recently developed in vivo methods have brought a different set of problems such as separation and purification of nanomaterials made in vivo. Here, a novel approach that harnesses cellular pathways for in vitro synthesis of high-quality tellurium nanorods with tunable lengths and optical properties is reported. It is first demonstrated that in vivo biochemical pathways could be used to synthesize Te nanorods via the intracellular reduction of TeO3(2-) in living Staphylococcus aureus cells. The pathways to set up a quasi-biological system for Te precursor formation are then utilized, which could further synthesize Te nanorods in vitro. This allows to successfully synthesize in vitro, under routine laboratory conditions, Te nanorods with uniform and tunable lengths, ranging from about 10 to 200 nm, and controllable optical properties with high molar extinction coefficients. The approach here should open new avenues for controllable, facile, and efficient synthesis of designer nanomaterials for diverse industrial and biomedical applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Synthesis and SAR studies of potent imidazopyridine anticoccidial agents.

    PubMed

    Liang, Gui-Bai; Qian, Xiaoxia; Feng, Dennis; Fisher, Michael; Brown, Christine M; Gurnett, Anne; Leavitt, Penny Sue; Liberator, Paul A; Misura, Andrew S; Tamas, Tamas; Schmatz, Dennis M; Wyvratt, Matthew; Biftu, Tesfaye

    2007-07-01

    Diaryl imidazo[1,2-a]pyridine derivatives, such as 6a and 7i, have been synthesized and found to be potent inhibitors of parasite PKG activity. The most potent compounds are the 7-isopropylaminomethyl analog 6a and 2-isopropylamino analog 7i. These compounds are also fully active in in vivo assay as anticoccidial agents at 25 ppm in feed.

  19. Microplasma-liquid interactions for nanomaterials synthesis

    NASA Astrophysics Data System (ADS)

    Patel, Jenish; Maguire, Paul; Mariotti, Davide

    2012-10-01

    Interactions of microplasmas with solid, liquid and/or gas precursors provide new pathways for the synthesis and surface-engineering of nanomaterials. This study is focused on the plasma-induced non-euqilibrium liquid-chemistry (PiLC) as an effective approach to synthesize colloidal metal nanoparticles without using any reducing/capping agents. Highly dispersed gold and silver nanoparticles (NPs) were synthesized in aqueous solutions without any capping agents which explore the opportunities to functionalize the surface of these surfactant-free metal NPs for a better device applications. In particular, various sizes (5 nm to 100 nm) and shapes (e.g. spherical, hexagonal, pentagonal, triangular, etc.) of the gold nanoparticles (AuNPs) were formed with different concentrations of gold precursor. Moreover, conductivity, pH and temperature of the solutions were measured before and after the plasma processing, in order to realize the basic chemistry initiated by plasma in/at liquid surface. Especially, to understand the basic reduction process of AuNPs synthesis by plasma, we measured the presence the of hydrogen peroxide (H2O2) which is believed to be a strong reductant for gold and for the first time we demonstrated experimentally that H2O2 is the key factor that reduces the gold precursor to AuNPs. These investigations create the opportunities to understand how these microplasmas can be effectively explored to other materials synthesis/processing.

  20. 7 CFR 3201.99 - Water clarifying agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Water clarifying agents. 3201.99 Section 3201.99... Designated Items § 3201.99 Water clarifying agents. (a) Definition. Products designed to clarify and improve the quality of water by reducing contaminants such as excess nitrites, nitrates, phosphates, ammonia...

  1. 7 CFR 3201.99 - Water clarifying agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Water clarifying agents. 3201.99 Section 3201.99... Designated Items § 3201.99 Water clarifying agents. (a) Definition. Products designed to clarify and improve the quality of water by reducing contaminants such as excess nitrites, nitrates, phosphates, ammonia...

  2. A facile synthesis of novel self-assembled gold nanorods designed for near-infrared imaging.

    PubMed

    Pan, Dipanjan; Pramanik, Manojit; Senpan, Angana; Wickline, Samuel A; Wang, Lihong V; Lanza, Gregory M

    2010-12-01

    Molecular imaging techniques now allow recognition of early biochemical, physiological, and anatomical changes before manifestation of gross pathological changes. Photoacoustic imaging represents a novel non-ionizing detection technique that combines the advantages of optical and ultrasound imaging. Noninvasive photoacoustic tomography (PAT) imaging in combination with nanoparticle-based contrast agents show promise in improved detection and diagnosis of cardiovascular and cancer related diseases. In this report, a novel strategy is introduced to achieve self-assembled colloidal gold nanorods, which are constrained to the vasculature. Gold nanorods (2-4 nm) were incorporated into the core of self-assembled lipid-encapsulated nanoparticles (sGNR) (approximately 130 nm), providing more than hundreds of gold atoms per nanoparticle of 20% colloid suspension. The physico-chemical characterization in solution and anhydrous state with analytical techniques demonstrated that the particles were spherical and highly mono dispersed. In addition to the synthesis and characterization, sensitive near-infrared photoacoustic detection was impressively demonstrated in vitro.

  3. A Facile Synthesis of Novel Self-Assembled Gold Nanorods Designed for Near-Infrared Imaging

    PubMed Central

    Pramanik, Manojit; Senpan, Angana; Wickline, Samuel A.; Lanza, Gregory M.

    2011-01-01

    Molecular imaging techniques now allow recognition of early biochemical, physiological, and anatomical Changes before manifestation of gross pathological changes. Photoacoustic imaging represents a novel non-ionizing detection technique that combines the advantages of optical and ultrasound imaging Noninvasive photoacoustic tomography (PAT) imaging in combination with nanoparticle-based contrast agents show promise in improved detection and diagnosis of cardio-vascular and cancer related diseases. In this report, a novel strategy is introduced to achieve self-assembled colloidal gold nanorods, which are constrained to the vasculature. Gold nanorods (2–4 nm) were incorporated into the core of self-assembled lipid-encapsulated nanoparticles (sGNR)(~130 nm), providing more than hundreds of gold atoms per nanoparticle of 20% colloid suspension. The physico-chemical characterization in solution and anhydrous state with analytical techniques demonstrated that the particles were spherical and highly mono dispersed. In addition to the synthesis and characterization, sensitive near-infrared photoacoustic detection was impressively demonstrated in vitro. PMID:21121304

  4. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--an update.

    PubMed

    Grunberg, Steven M; Osoba, David; Hesketh, Paul J; Gralla, Richard J; Borjeson, Sussanne; Rapoport, Bernardo L; du Bois, Andreas; Tonato, Maurizio

    2005-02-01

    Development of effective antiemetic therapy depends upon an understanding of both the antiemetic agents and the emetogenic challenges these agents are designed to address. New potential antiemetic agents should be studied in an orderly manner, proceeding from phase I to phase II open-label trials and then to randomized double-blind phase III trials comparing new agents and regimens to best standard therapy. Use of placebos in place of antiemetic therapy against highly or moderately emetogenic chemotherapy is unacceptable. Nausea and vomiting should be evaluated separately and for both the acute and delayed periods. Defining the emetogenicity of new antineoplastic agents is a challenge, since such data are often not reliably recorded during early drug development. A four-level classification system is proposed for emetogenicity of intravenous antineoplastic agents. A separate four-level classification system for emetogenicity of oral antineoplastic agents, which are often given over an extended period of time, is also proposed.

  5. Drug Design Relating Amebicides to Inhibition of Protein Synthesis.

    DTIC Science & Technology

    1977-09-01

    A study of the effect of emetine on protein synthesis in E. histolytica was made on log phase amebas as compared to stationary phase amebas ...Sensitivity to emetine was maintained independently of the rate of protein synthesis. Furthermore, both stages of amebas had the same capacity to bind emetine...elongation site. Finally, evidence was obtained that the capacity to bind emetine provides a basis for conferring drug resistance in amebas . A direct

  6. Designing Selectivity in Metal-Semiconductor Nanocrystals: Synthesis, Characterization, and Self-Assembly

    NASA Astrophysics Data System (ADS)

    Pavlopoulos, Nicholas George

    This dissertation contains six chapters detailing recent advances that have been made in the synthesis and characterization of metal-semiconductor hybrid nanocrystals (HNCs), and the applications of these materials. Primarily focused on the synthesis of well-defined II-VI semiconductor nanorod (NR) and tetrapod (TP) based constructs of interest for photocatalytic and solar energy applications, the research described herein discusses progress towards the realization of key design rules for the synthesis of functional semiconductor nanocrystals (NCs). As such, a blend of novel synthesis, advanced characterization, and direct application of heterostructured nanoparticles are presented. The first chapter is a review summarizing the design, synthesis, properties, and applications of multicomponent nanomaterials composed of disparate semiconductor and metal domains. By coupling two compositionally distinct materials onto a single nanocrystal, synergistic properties can arise that are not present in the isolated components, ranging from self-assembly to photocatalysis. For semiconductor nanomaterials, this was first realized in the ability to tune nanomaterial dimensions from 0-D quantum dot (QD) structures to cylindrical (NR) and branched (TP) structures by exploitation of advanced colloidal synthesis techniques and understandings of NC facet reactivities. The second chapter is focused on the synthesis and characterization of well-defined CdSe-seeded-CdS (CdSe CdS) NR systems synthesized by overcoating of wurtzite (W) CdSe quantum dots with W-CdS shells. 1-dimensional NRs have been interesting constructs for applications such as solar concentrators, optical gains, and photocatalysis. Through synthetic control over CdSe CdS NR systems, materials with small and large CdSe seeds were prepared, and for each seed size, multiple NR lengths were prepared. Through transient absorption studies, it was found that band alignment did not affect the efficiency of charge localization

  7. Hierarchical macro-mesoporous structures in the system TiO{sub 2}-Al{sub 2}O{sub 3}, obtained by hydrothermal synthesis using Tween-20 as a directing agent

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

    Garcia-Benjume, M.L.; Espitia-Cabrera, M.I.; Contreras-Garcia, M.E., E-mail: eucontre@zeus.umich.mx

    2009-12-15

    Macro-mesoporous powders of titania, alumina, and mixed titania-20%alumina systems were obtained by hydrothermal synthesis employing surfactant Tween-20 as structural directing agent in order to promote the textural properties of titania. The effect of the alumina in the titania phase and on textural properties was analyzed. The obtained powders presented a macroporous channel structure that was characterized by X-ray diffractometry, scanning and transmission electron microscopy, N{sub 2} adsorption-desorption analysis, pore size distribution, Fourier transform infrared spectrometry, and thermogravimetric analysis. It was found that alumina content retarded the anatase phase crystallization and increased the Brunauer-Emmet-Teller surface area from 136 to 210 m{supmore » 2}/g. The powders calcined at 400 deg. C are thermally stable and possess an interconnected macro-mesoporous hierarchical structure; the results indicate that this synthesis can be employed to prepare mixed titania-alumina with good textural properties.« less

  8. Learning Sequences of Actions in Collectives of Autonomous Agents

    NASA Technical Reports Server (NTRS)

    Turner, Kagan; Agogino, Adrian K.; Wolpert, David H.; Clancy, Daniel (Technical Monitor)

    2001-01-01

    In this paper we focus on the problem of designing a collective of autonomous agents that individually learn sequences of actions such that the resultant sequence of joint actions achieves a predetermined global objective. We are particularly interested in instances of this problem where centralized control is either impossible or impractical. For single agent systems in similar domains, machine learning methods (e.g., reinforcement learners) have been successfully used. However, applying such solutions directly to multi-agent systems often proves problematic, as agents may work at cross-purposes, or have difficulty in evaluating their contribution to achievement of the global objective, or both. Accordingly, the crucial design step in multiagent systems centers on determining the private objectives of each agent so that as the agents strive for those objectives, the system reaches a good global solution. In this work we consider a version of this problem involving multiple autonomous agents in a grid world. We use concepts from collective intelligence to design goals for the agents that are 'aligned' with the global goal, and are 'learnable' in that agents can readily see how their behavior affects their utility. We show that reinforcement learning agents using those goals outperform both 'natural' extensions of single agent algorithms and global reinforcement, learning solutions based on 'team games'.

  9. Instrument Modeling and Synthesis

    NASA Astrophysics Data System (ADS)

    Horner, Andrew B.; Beauchamp, James W.

    During the 1970s and 1980s, before synthesizers based on direct sampling of musical sounds became popular, replicating musical instruments using frequency modulation (FM) or wavetable synthesis was one of the “holy grails” of music synthesis. Synthesizers such as the Yamaha DX7 allowed users great flexibility in mixing and matching sounds, but were notoriously difficult to coerce into producing sounds like those of a given instrument. Instrument design wizards practiced the mysteries of FM instrument design.

  10. New peptide deformylase inhibitors design, synthesis and pharmacokinetic assessment.

    PubMed

    Lv, Fengping; Chen, Chen; Tang, Yang; Wei, Jianhai; Zhu, Tong; Hu, Wenhao

    2016-08-01

    The docking approach for the screening of designed small molecule ligands, led to the identification of a critical arginine residue in peptide deformylase for spiro cyclopropyl PDF inhibitor's extra hydrophobic binding, providing us a useful tool for searching more efficient PDF inhibitors to fight for horrifying antibiotics resistance. Further synthetic modification was undertaken to optimize the potency of amide compounds. To lower metabolic susceptibility and in turn reduce unwanted metabolic toxicity that was observed clinically, while retaining desired antibacterial activity, the use of azoles as amide bioisosteres had also been investigated. After the completion of chemical synthesis, all the compounds were evaluated through in vitro antibacterial activity assay, some of which were further subject to in vivo rat pharmacokinetic assessment. Those findings in this letter showed that spiro cyclopropyl proline N-formyl hydroxylamines, and especially the bioisosteric azoles, can represent a promising class of PDF inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Design and Synthesis of Potent Quillaja Saponin Vaccine Adjuvants

    PubMed Central

    Adams, Michelle M.; Damani, Payal; Perl, Nicholas R.; Won, Annie; Hong, Feng

    2010-01-01

    The success of antitumor and antiviral vaccines often requires the use of an adjuvant, a substance that significantly enhances the immune response to a co-administered antigen. Only a handful of adjuvants have both sufficient potency and acceptable toxicity for clinical investigation. One promising adjuvant is QS-21, a saponin natural product that is the immunopotentiator of choice in many cancer and infectious disease vaccine clinical trials. However, the therapeutic promise of QS-21 adjuvant is curtailed by several factors, including its scarcity, difficulty in purification to homogeneity, dose-limiting toxicity, and chemical instability. Here we report the design, synthesis, and evaluation of chemically stable synthetic saponins. These novel, amide-modified, non-natural substances exhibit immunopotentiating effects in vivo that rival or exceed that of QS-21 in evaluations with the GD3-KLH melanoma conjugate vaccine. The highly convergent synthetic preparation of these novel saponins establishes new avenues for discovering improved molecular adjuvants for specifically tailored vaccine therapies. PMID:20088518

  12. Multimedia Learning in an Interactive Self-Explaining Environment: What Works in the Design of Agent-Based Microworlds?

    ERIC Educational Resources Information Center

    Mayer, Richard E.; Dow, Gayle T.; Mayer, Sarah

    2003-01-01

    Students learned about electric motors by asking questions and receiving answers from an on-screen pedagogical agent named Dr. Phyz who stood next to an on-screen drawing of an electric motor. Results are consistent with a cognitive theory of multimedia learning and yield principles for the design of interactive multimedia learning environments.…

  13. Super-secondary structure peptidomimetics: design and synthesis of an α-α hairpin analogue

    PubMed Central

    Nevola, Laura; Rodriguez, Johanna M.; Thompson, Sam; Hamilton, Andrew D.

    2015-01-01

    The α-α helix motif presents key recognition domains in protein-protein and protein-oligonucleotide binding, and is one of the most common super-secondary structures. Herein we describe the design, synthesis and structural characterization of an α-α hairpin analogue based on a tetra-coordinated Pd(II) bis-(iminoisoquinoline) complex as a template for the display of two α-helix mimics. This approach is exemplified by the attachment of two biphenyl peptidomimetics to reproduce the side-chains of the i and i+4 residues of two helices. PMID:26052191

  14. Design, synthesis, and evaluation of inhibitors of trypanosomal and leishmanial dihydrofolate reductase.

    PubMed

    Chowdhury, S F; Villamor, V B; Guerrero, R H; Leal, I; Brun, R; Croft, S L; Goodman, J M; Maes, L; Ruiz-Perez, L M; Pacanowska, D G; Gilbert, I H

    1999-10-21

    This paper concerns the design, synthesis, and evaluation of inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Initially study was made of the structures of the leishmanial and human enzyme active sites to see if there were significant differences which could be exploited for selective drug design. Then a series of compounds were synthesized based on 5-benzyl-2, 4-diaminopyrimidines. These compounds were assayed against the protozoan and human enzymes and showed selectivity for the protozoan enzymes. The structural data was then used to rationalize the enzyme assay data. Compounds were also tested against the clinically relevant forms of the intact parasite. Activity was seen against the trypanosomes for a number of compounds. The compounds were in general less active against Leishmania. This latter result may be due to uptake problems. Two of the compounds also showed some in vivo activity in a model of African trypanosomiasis.

  15. Design and Stereoselective Preparation of a New Class of Chiral Olefin Metathesis Catalysts and Application to Enantioselective Synthesis of Quebrachamine: Catalyst Development Inspired by Natural Product Synthesis

    PubMed Central

    Sattely, Elizabeth S.; Meek, Simon J.; Malcolmson, Steven J.; Schrock, Richard R.; Hoveyda, Amir H.

    2010-01-01

    A total synthesis of the Aspidosperma alkaloid quebrachamine in racemic form is first described. A key catalytic ring-closing metathesis of an achiral triene is used to establish the all-carbon quaternary stereogenic center and the tetracyclic structure of the natural product; the catalytic transformation proceeds with reasonable efficiency through the use of existing achiral Ru or Mo catalysts. Ru- or Mo-based chiral olefin metathesis catalysts have proven to be inefficient and entirely nonselective in cases where the desired product is observed. In the present study, the synthesis route thus serves as a platform for the discovery of new olefin metathesis catalysts that allow for efficient completion of an enantioselective synthesis of quebrachamine. Accordingly, on the basis of mechanistic principles, stereogenic-at-Mo complexes bearing only monodentate ligands have been designed. The new catalysts provide significantly higher levels of activity than observed with the previously reported Ru- or Mo-based complexes. Enantiomerically enriched chiral alkylidenes are generated through diastereoselective reactions involving achiral Mo-based bispyrrolides and enantiomerically pure silyl-protected binaphthols. Such chiral catalysts initiate the key enantioselective ring-closing metathesis step in the total synthesis of quebrachamine efficiently (1 mol % loading, 22 °C, 1 h, >98% conversion, 84% yield) and with high selectivity (98:2 er, 96% ee). PMID:19113867

  16. The Hermod Behavioral Synthesis System

    DTIC Science & Technology

    1988-06-08

    LDescription 1 lib tech-independent Transformation & Parser Optimization lib Hardware • g - utSynhesze Generator li Datapath lb Hardware liCotllb...Proc. 22nd Design Automation Conference, ACM/IEEE, June 1985, pp. 475-481. [7] G . De Micheli, "Synthesis of Control Systems", in Design Systems for...VLSI Circuits: Logic Synthesis and Silicon Compilation, G . De Micheli, A. Sangiovanni-Vincentelli, and P. Antognetti, (editor), Martinus Nijhoff

  17. Excessive and addictive gaming control using counselling agent in online game design

    NASA Astrophysics Data System (ADS)

    Ididi, Italumeh O.; Hassan, Sa'adah; Ghani, Abdul Azim Abd; Ali, Norhayati Mohd

    2017-10-01

    In recent times, online game play has become a food for thought to concerned individuals, researchers and authorities of various countries due to its excessive and addictive usage. Although, various government have taken certain measures such as shutting down internet cafe at certain hours of the day, censoring the most brutal, offensive and aggressive sections of certain games before they are released. Researchers have advised developers on ways of limiting harm on players by suggesting design changes on time limit. Furthermore, researchers have also suggested that online game distributors ought to make available appropriate referral services. The impart of the above are yet to make any remarkable impact on players. In this paper, we have proposed a Counseling Agent model integrating informative and self-appraisal messages in online game design as a control measure. Informative and self-appraisal messaging in games have proven optimistic through making positive impact on player's thoughts and behavior towards gaming. These messages are expected to remind players about the negative impact of excessive and addictive gaming habits, as well as suggesting possible reductive solutions through message streaming.

  18. Molecular Docking, Synthesis And Biological Evaluation Of Sulphonylureas/Guanidine Derivatives As Promising Antidiabetics Agent.

    PubMed

    Panchal, Ishan; Sen, Dhrubo Jyoti; Patel, Ashish D; Shah, Umang; Patel, Mehul; Navle, Archana; Bhavsar, Vashisth

    2017-10-02

    A series of novel sulphonylureas/guanidine derivatives were designed, synthesized, and evaluated for the treatment of diabetes mellitus. In this study, the designed compounds were docked with AKR1C1 complexes by using glide docking program and docking calculations were performed to predict the binding affinity of the designed compounds with the binding pocket of protein 4YVP and QikProp program was used to predict the ADME/T properties of the analogues. All the targeted derivatives were synthesized and purified by recrystallization. Synthesize compounds were characterized by various physicochemical and various spectroscopic techniques like melting point, thin layer chromatography, infrared spectroscopy (KBr pellets), mass spectroscopy(m/z), 1H NMR (DMSO-d6), and 13C NMR. The synthesized compounds were further studied for biological evolution by alloxan (150 mg/dl, intraperitonial) induced diabetic rat model for in-vivo studies. Among all the synthesized derivatives, 5c and 5d were most potent as per binding energy. Compound 5i have shown a better plasma glucose reduction compared to glibenclamide. Hence, it will further use as a lead compound to develop a more such kind of agent. The docking study revealed that in all designed sulphonylureas/guanidine series of compounds 5c and 5d were found to be most potent compounds as per the binding energy compared to glibenclamide. With the help of details study of in vivo biological activity we observed that compound 5i gives better result compared to glibenclamide as standard. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Rational Design and Synthesis of Carboxylate Gemini Surfactants with an Excellent Aggregate Behavior for Nano-La2O3 Morphology-Controllable Preparation.

    PubMed

    Liao, Xueming; Gao, Zhinong; Xia, Yan; Niu, Fei; Zhai, Wenzhong

    2017-04-04

    A series of carboxylate gemini surfactants (CGS, C n -Φ-C n , n = 12, 14, 16, 18) with diphenyl ketone as a spacer group were prepared using a simple and feasible synthetic method. These CGS exhibited an excellent surface activity with extremely low critical micelle concentration (CMC) value (approximately 10 -5 mol/L), good performance in reducing surface tension (nearly 30 mN/m), and the ability of molecular self-assembly into different aggregate morphologies via adjusting the concentrations, which is attributed to the introduction of diphenyl ketone and carboxylic acid ammonium salt in the molecular structure. Moreover, the surface activity and self-assembly ability of CGS were further optimized by tuning the length of the tail chain. These excellent properties imply that CGS can be a soft template to prepare nanomaterials, especially in morphology-controllable synthesis. By adjusting the concentration of one of CGS (C 12 -Φ-C 12 ), nano-La 2 O 3 particles with diverse morphologies were obtained, including spherical shape, bead-chain shape, rod shape, velvet-antler shape, cedar shape, and bowknot shape. This work offers a vital insight into the rational design of template agents for the development of morphology-controllable nanomaterials.

  20. Using Animated Agents in Learner-Controlled Training: The Effects of Design Control

    ERIC Educational Resources Information Center

    Behrend, Tara S.; Thompson, Lori Foster

    2012-01-01

    Animated agents have the potential to increase engagement and learning during online training by acting as personalized tutors. However, little is known about the conditions that make these agents most effective. In this study, 183 e-learners completed a Microsoft Excel training course. Approximately half were assigned an agent with predetermined…