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Sample records for agents show promise

  1. Pembrolizumab Shows Promise for NSCLC.

    PubMed

    2015-06-01

    Data from the KEYNOTE-001 trial show that pembrolizumab improves clinical outcomes for patients with advanced non-small cell lung cancer, and is well tolerated. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy.

  2. Cobalt Derivatives as Promising Therapeutic Agents

    PubMed Central

    Heffern, Marie C.; Yamamoto, Natsuho; Holbrook, Robert J.; Eckermann, Amanda L.; Meade, Thomas J.

    2013-01-01

    Inorganic complexes are versatile platforms for the development of potent and selective pharmaceutical agents. Cobalt possesses a diverse array of properties that can be manipulated to yield promising drug candidates. Investigations into the mechanism of cobalt therapeutic agents can provide valuable insight into the physicochemical properties that can be harnessed for drug development. This review presents examples of bioactive cobalt complexes with special attention to their mechanisms of action. Specifically, cobalt complexes that elicit biological effects through protein inhibition, modification of drug activity, and bioreductive activation are discussed. Insights gained from these examples reveal features of cobalt that can be rationally tuned to produce therapeutics with high specificity and improved efficacy for the biomolecule or pathway of interest. PMID:23270779

  3. Cancer Drug Shows Early Promise for Parkinson's Disease

    MedlinePlus

    ... 159834.html Cancer Drug Shows Early Promise for Parkinson's Disease Medication was generally found safe, and study ... initial signs of promise for advanced cases of Parkinson's disease, researchers are reporting. Experts stressed that the ...

  4. New Drug Shows Promise for Rare Blood Cancers

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159626.html New Drug Shows Promise for Rare Blood Cancers Organ ... exist for people with advanced mastocytosis. So the new findings are "a real advance," said Hromas, who ...

  5. Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder

    MedlinePlus

    ... 1999 Spotlight on Research 2014 February 2014 (historical) Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder Replacing a protein that is crucial to ensuring that the skin’s ...

  6. Experimental Immune Cell Rx Shows Promise for Leukemia

    MedlinePlus

    ... The NK therapy is a new form of "immunotherapy" -- which refers to any treatment that harnesses the ... system's natural tumor-fighting abilities. Other types of immunotherapy have already been showing promise against various types ...

  7. Salivary Gland Biopsy Shows Promise to Helping to Diagnose Parkinson's

    MedlinePlus

    ... Parkinson's HelpLine Learn More Science News Salivary Gland Biopsy Shows Promise to Helping to Diagnose Parkinson’s - Mar ... team performed a procedure called a needle core biopsy of the submandibular glands in 15 people who ...

  8. Experimental Lung Cancer Drug Shows Early Promise | Poster

    Cancer.gov

    By Frank Blanchard, Staff Writer A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy. The drug, CO-1686, performed well in a preclinical study involving xenograft and transgenic mice, as reported in the journal Cancer Discovery. It is now being evaluated for safety and efficacy in Phase I and II clinical trials.

  9. Amaryllidaceae Isocarbostyril Alkaloids and Their Derivatives as Promising Antitumor Agents

    PubMed Central

    Ingrassia, Laurent; Lefranc, Florence; Mathieu, Véronique; Darro, Francis; Kiss, Robert

    2008-01-01

    This review covers the isolation, total synthesis, biologic activity, and more particularly the in vitro and in vivo antitumor activities of naturally occurring isocarbostyril alkaloids from the Amaryllidaceae family. Starting from these natural products, new derivatives have been synthesized to explore structure-activity relationships within the chemical class and to obtain potential candidates for preclinical development. This approach appears to be capable of providing novel promising anticancer agents. PMID:18607503

  10. Drug Shows Promise Against MS in Mouse Study

    MedlinePlus

    ... a news release from the American Academy of Neurology. A healthy immune system has T cells and ... findings showed. Dr. Paul Wright is chair of neurology at North Shore University Hospital in Manhasset, N. ...

  11. Shogaols from Zingiber officinale as promising antifouling agents.

    PubMed

    Etoh, Hideo; Kondoh, Takeyoshi; Noda, Rikoh; Singh, Inder Pal; Sekiwa, Yohko; Morimitsu, Kohjiro; Kubota, Kikue

    2002-08-01

    We isolated the highly potent attachment-inhibitors (three times more active than standard CuSO4 in the blue mussel assay), trans-6-, 8-, and 10-shogaols, from a hexane extract of the roots of ginger, Zingiber officinale Roscoe. Trans-8-shogaol showed the highest antifouling activity comparable with that of tributyltin fluoride (TBTF), which is recognized as one of the most effective antifouling agents, in the conventional submerged assay. PMID:12353640

  12. Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase.

    PubMed

    Mathieu, Véronique; Chantôme, Aurélie; Lefranc, Florence; Cimmino, Alessio; Miklos, Walter; Paulitschke, Verena; Mohr, Thomas; Maddau, Lucia; Kornienko, Alexander; Berger, Walter; Vandier, Christophe; Evidente, Antonio; Delpire, Eric; Kiss, Robert

    2015-10-01

    Despite the recent advances in the treatment of tumors with intrinsic chemotherapy resistance, such as melanoma and renal cancers, their prognosis remains poor and new chemical agents with promising activity against these cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose anticancer potential had previously received little attention, was isolated from Diplodia cupressi and found to display specific anticancer activity in vitro against melanoma and kidney cancer subpanels in the National Cancer Institute (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 µM and a cellular sensitivity profile that did not match that of any other agent in the 765,000 compound database. Subsequent mechanistic studies in melanoma and other multidrug-resistant in vitro cancer models showed that sphaeropsidin A can overcome apoptosis as well as multidrug resistance by inducing a marked and rapid cellular shrinkage related to the loss of intracellular Cl(-) and the decreased HCO3 (-) concentration in the culture supernatant. These changes in ion homeostasis and the absence of effects on the plasma membrane potential were attributed to the sphaeropsidin A-induced impairment of regulatory volume increase (RVI). Preliminary results also indicate that depending on the type of cancer, the sphaeropsidin A effects on RVI could be related to Na-K-2Cl electroneutral cotransporter or Cl(-)/HCO3 (-) anion exchanger(s) targeting. This study underscores the modulation of ion-transporter activity as a promising therapeutic strategy to combat drug-resistant cancers and identifies the fungal metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI in cancer cells. PMID:25868554

  13. Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase

    PubMed Central

    Mathieu, Véronique; Chantôme, Aurélie; Lefranc, Florence; Cimmino, Alessio; Miklos, Walter; Paulitschke, Verena; Mohr, Thomas; Maddau, Lucia; Kornienko, Alexander; Berger, Walter; Vandier, Christophe; Evidente, Antonio; Delpire, Eric; Kiss, Robert

    2016-01-01

    Despite the recent advances in the treatment of tumors with intrinsic chemotherapy resistance, such as melanoma and renal cancers, their prognosis remains poor and new chemical agents with promising activity against these cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose anticancer potential had previously received little attention, was isolated from Diplodia cupressi and found to display specific anticancer activity in vitro against melanoma and kidney cancer subpanels in the National Cancer Institute (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 μM and a cellular sensitivity profile that did not match that of any other agent in the 765,000 compound database. Subsequent mechanistic studies in melanoma and other multidrug-resistant in vitro cancer models showed that sphaeropsidin A can overcome apoptosis as well as multidrug resistance by inducing a marked and rapid cellular shrinkage related to the loss of intracellular Cl− and the decreased HCO3− concentration in the culture supernatant. These changes in ion homeostasis and the absence of effects on the plasma membrane potential were attributed to the sphaeropsidin A-induced impairment of regulatory volume increase (RVI). Preliminary results also indicate that depending on the type of cancer, the sphaeropsidin A effects on RVI could be related to Na–K–2Cl electroneutral cotransporter or Cl−/HCO3− anion exchanger(s) targeting. This study underscores the modulation of ion-transporter activity as a promising therapeutic strategy to combat drug-resistant cancers and identifies the fungal metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI in cancer cells. PMID:25868554

  14. New promising anticancer agents in development: what comes next?

    PubMed

    Verweij, J

    1996-01-01

    Anticancer drug development has recently shifted in part to development of more innovative anticancer agents. The increasing knowledge of the pathogenetic mechanisms involved in cancer cell growth has enabled the introduction of drug screening that is more mechanism-based. The realization that new targets should be preferentially evaluated as sites for anticancer drug treatment has led to the introduction of drugs such as the taxanes. Following this logic, several new drugs are being developed. Minor groove-binding agents such as carzelesin and oral platins lacking organ toxicity, such as JM216, have recently entered clinical studies. The activity of gemcitabine is a result of its being a cytidine analogue and being competitively incorporated by DNA; the drug has shown interesting activity in non-small-cell lung cancer and, although registration is imminent, issues regarding the optimal dose and administration schedule have yet to be resolved. Tomudex is a thymidylate synthase inhibitor with interesting activity in colorectal cancer. Activity in colorectal cancer is also of interest for irinotecan, the first clinically applied topoisomerase I inhibitor, an enzyme that is another example of a new target for anticancer drugs. Irinotecan has produced consistent response rates of 20-30% in six different studies in colorectal cancer. The other topoisomerase I inhibitor that is in the advanced stage of development is topotecan. This drug has shown activity in second-line chemotherapy for ovarian cancer and small-cell lung cancer. Another interesting feature of topotecan is the availability of an oral formulation with consistent bioavailability. Drugs interfering with cellular signal transduction, such as the protein kinase C inhibitors, are in the development spotlight. Finally, the use of old drugs in new ways, such as immunoconjugates of doxorubicin, holds promise for the near future. PMID:8765408

  15. Promises and failures of gallium as an antibacterial agent.

    PubMed

    Minandri, Fabrizia; Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco; Visca, Paolo

    2014-01-01

    Gallium has a long history as a diagnostic and chemotherapeutic agent. The pharmacological properties of Ga(III) rely on chemical mimicry; when Ga(III) is exogenously supplied to living cells it can replace Fe(III) within target molecules, thereby perturbing bacterial metabolism. Ga(III)-induced metabolic distresses are dramatic in fast-growing cells, like bacterial cells. Interest in the antibacterial properties of Ga(III) has been raised by the compelling need for novel drugs to combat multidrug-resistant bacteria and by the shortage of new antibiotic candidates in the pharmaceutical pipeline. Ga(III) activity has been demonstrated, both in vitro and in animal models of infections, on several bacterial pathogens, also including intracellular and biofilm-forming bacteria. Ga(III) activity is affected by iron availability and the metabolic state of the cell, being maximal in iron-poor media and in respiring cells. Synergism between Ga(III) and antibiotics holds promise as last resort therapy for infections sustained by pandrug-resistant bacteria.

  16. Modified Gadonanotubes as a promising novel MRI contrasting agent

    PubMed Central

    2013-01-01

    Background and purpose of the study Carbon nanotubes (CNTs) are emerging drug and imaging carrier systems which show significant versatility. One of the extraordinary characteristics of CNTs as Magnetic Resonance Imaging (MRI) contrasting agent is the extremely large proton relaxivities when loaded with gadolinium ion (Gdn3+) clusters. Methods In this study equated Gdn3+ clusters were loaded in the sidewall defects of oxidized multiwalled (MW) CNTs. The amount of loaded gadolinium ion into the MWCNTs was quantified by inductively coupled plasma (ICP) method. To improve water solubility and biocompatibility of the system, the complexes were functionalized using diamine-terminated oligomeric poly (ethylene glycol) via a thermal reaction method. Results Gdn3+ loaded PEGylated oxidized CNTs (Gdn3+@CNTs-PEG) is freely soluble in water and stable in phosphate buffer saline having particle size of about 200 nm. Transmission electron microscopy (TEM) images clearly showed formation of PEGylated CNTs. MRI analysis showed that the prepared solution represents 10% more signal intensity even in half concentration of Gd3+ in comparison with commerciality available contrasting agent Magnevist®. In addition hydrophilic layer of PEG at the surface of CNTs could prepare stealth nanoparticles to escape RES. Conclusion It was shown that Gdn3+@CNTs-PEG was capable to accumulate in tumors through enhanced permeability and retention effect. Moreover this system has a potential for early detection of diseases or tumors at the initial stages. PMID:23815852

  17. Alkanediamide-Linked Bisbenzamidines Are Promising Antiparasitic Agents.

    PubMed

    Vanden Eynde, Jean J; Mayence, Annie; Mottamal, Madhusoodanan; Bacchi, Cyrus J; Yarlett, Nigel; Kaiser, Marcel; Brun, Reto; Huang, Tien L

    2016-01-01

    A series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two Trypanosoma brucei (T.b.) subspecies: T.b. brucei and T.b. rhodesiense, Trypanosoma cruzi, Leishmania donovani and two Plasmodium falciparum subspecies: a chloroquine-sensitive strain (NF54) and a chloroquine-resistant strain (K1). The in vitro cytotoxicity was determined against rat myoblast cells (L6). Seven compounds (5, 6, 10, 11, 12, 14, 15) showed high potency against both strains of T. brucei and P. falciparum with the inhibitory concentrations for 50% (IC50) in the nanomolar range (IC50 = 1-96 nM). None of the tested derivatives was significantly active against T. cruzi or L. donovani. Three of the more potent compounds (5, 6, 11) were evaluated in vivo in mice infected with the drug-sensitive (Lab 110 EATRO and KETRI 2002) or drug-resistant (KETRI 2538 and KETRI 1992) clinical isolates of T. brucei. Compounds 5 and 6 were highly effective in curing mice infected with the drug-sensitive strains, including a drug-resistant strain KETRI 2538, but were ineffective against KETRI 1992. Thermal melting of DNA and molecular modeling studies indicate AT-rich DNA sequences as possible binding sites for these compounds. Several of the tested compounds are suitable leads for the development of improved antiparasitic agents. PMID:27104545

  18. Alkanediamide-Linked Bisbenzamidines Are Promising Antiparasitic Agents

    PubMed Central

    Vanden Eynde, Jean J.; Mayence, Annie; Mottamal, Madhusoodanan; Bacchi, Cyrus J.; Yarlett, Nigel; Kaiser, Marcel; Brun, Reto; Huang, Tien L.

    2016-01-01

    A series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two Trypanosoma brucei (T.b.) subspecies: T.b. brucei and T.b. rhodesiense, Trypanosoma cruzi, Leishmania donovani and two Plasmodium falciparum subspecies: a chloroquine-sensitive strain (NF54) and a chloroquine-resistant strain (K1). The in vitro cytotoxicity was determined against rat myoblast cells (L6). Seven compounds (5, 6, 10, 11, 12, 14, 15) showed high potency against both strains of T. brucei and P. falciparum with the inhibitory concentrations for 50% (IC50) in the nanomolar range (IC50 = 1–96 nM). None of the tested derivatives was significantly active against T. cruzi or L. donovani. Three of the more potent compounds (5, 6, 11) were evaluated in vivo in mice infected with the drug-sensitive (Lab 110 EATRO and KETRI 2002) or drug-resistant (KETRI 2538 and KETRI 1992) clinical isolates of T. brucei. Compounds 5 and 6 were highly effective in curing mice infected with the drug-sensitive strains, including a drug-resistant strain KETRI 2538, but were ineffective against KETRI 1992. Thermal melting of DNA and molecular modeling studies indicate AT-rich DNA sequences as possible binding sites for these compounds. Several of the tested compounds are suitable leads for the development of improved antiparasitic agents. PMID:27104545

  19. Catalytic bioscavengers in nerve agent poisoning: A promising approach?

    PubMed

    Worek, Franz; Thiermann, Horst; Wille, Timo

    2016-02-26

    The repeated use of the nerve agent sarin against civilians in Syria in 2013 emphasizes the continuing threat by chemical warfare agents. Multiple studies demonstrated a limited efficacy of standard atropine-oxime treatment in nerve agent poisoning and called for the development of alternative and more effective treatment strategies. A novel approach is the use of stoichiometric or catalytic bioscavengers for detoxification of nerve agents in the systemic circulation prior to distribution into target tissues. Recent progress in the design of enzyme mutants with reversed stereo selectivity resulting in improved catalytic activity and their use in in vivo studies supports the concept of catalytic bioscavengers. Yet, further research is necessary to improve the catalytic activity, substrate spectrum and in vivo biological stability of enzyme mutants. The pros and cons of catalytic bioscavengers will be discussed in detail and future requirements for the development of catalytic bioscavengers will be proposed.

  20. Curcumin: a promising agent targeting cancer stem cells.

    PubMed

    Zang, Shufei; Liu, Tao; Shi, Junping; Qiao, Liang

    2014-01-01

    Cancer stem cells are a subset of cells that are responsible for cancer initiation and relapse. They are generally resistant to the current anticancer agents. Successful anticancer therapy must consist of approaches that can target not only the differentiated cancer cells, but also cancer stem cells. Emerging evidence suggested that the dietary agent curcumin exerted its anti-cancer activities via targeting cancer stem cells of various origins such as those of colorectal cancer, pancreatic cancer, breast cancer, brain cancer, and head and neck cancer. In order to enhance the therapeutic potential of curcumin, this agent has been modified or used in combination with other agents in the experimental therapy for many cancers. In this mini-review, we discussed the effect of curcumin and its derivatives in eliminating cancer stem cells and the possible underlying mechanisms.

  1. Newly developed foam ceramic body shows promise as thermal insulation material at 3000 deg F

    NASA Technical Reports Server (NTRS)

    Blocker, E. W.; Paul, R. D.

    1967-01-01

    Optimized zirconia foam ceramic body shows promise for use as a thermal insulation material. The insulating media displays low density and thermal conductivity, good thermal shock resistance, high melting point, and mechanical strength.

  2. Antibody mimetics: promising complementary agents to animal-sourced antibodies.

    PubMed

    Baloch, Abdul Rasheed; Baloch, Abdul Wahid; Sutton, Brian J; Zhang, Xiaoying

    2016-01-01

    Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed.

  3. Antibody mimetics: promising complementary agents to animal-sourced antibodies.

    PubMed

    Baloch, Abdul Rasheed; Baloch, Abdul Wahid; Sutton, Brian J; Zhang, Xiaoying

    2016-01-01

    Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed. PMID:25264572

  4. Decitabine: a promising epi-immunotherapeutic agent in solid tumors.

    PubMed

    Li, Xiang; Mei, Qian; Nie, Jing; Fu, Xiaobing; Han, Weidong

    2015-03-01

    The incidence of malignancies is increasing worldwide. Despite early detection, surgical resection, chemotherapy and radiotherapy, numerous patients continue to die from metastasis or recurrence. The immune system has the capacity to eradicate cancer cells; however, many tumors, especially solid tumors, present considerable challenges that render immune cells ineffectual, making cancer cells almost 'invisible' to the immune system. Compelling evidence has demonstrated that DNA methylation is involved in tumor development and progression, leading to the impaired immunogenicity and immune recognition of cancer cells. The hypomethylating agent decitabine has been shown to have therapeutic effects in malignancies and exhibits an effective immune efficacy in eliminating cancer cells. Based on the hypomethylating and immune remodeling effects of decitabine, we propose in this review that decitabine can be considered an epi-immunotherapeutic agent. We summarize the results of recent preclinical studies and clinical trials for decitabine and discuss the connections among its hypomethylating effect, immune-activated mechanisms and clinical activity in solid tumors, keeping in mind the goal of optimizing dosing schedules.

  5. Three New Escherichia coli Phages from the Human Gut Show Promising Potential for Phage Therapy.

    PubMed

    Dalmasso, Marion; Strain, Ronan; Neve, Horst; Franz, Charles M A P; Cousin, Fabien J; Ross, R Paul; Hill, Colin

    2016-01-01

    With the emergence of multi-drug resistant bacteria the use of bacteriophages (phages) is gaining renewed interest as promising anti-microbial agents. The aim of this study was to isolate and characterize phages from human fecal samples. Three new coliphages, ɸAPCEc01, ɸAPCEc02 and ɸAPCEc03, were isolated. Their phenotypic and genomic characteristics, and lytic activity against biofilm, and in combination with ciprofloxacin, were investigated. All three phages reduced the growth of E. coli strain DPC6051 at multiplicity of infection (MOI) between 10-3 and 105. A cocktail of all three phages completely inhibited the growth of E. coli. The phage cocktail also reduced biofilm formation and prevented the emergence of phage-resistant mutants which occurred with single phage. When combined with ciprofloxacin, phage alone or in cocktail inhibited the growth of E. coli and prevented the emergence of resistant mutants. These three new phages are promising biocontrol agents for E. coli infections. PMID:27280590

  6. Three New Escherichia coli Phages from the Human Gut Show Promising Potential for Phage Therapy

    PubMed Central

    Dalmasso, Marion; Strain, Ronan; Neve, Horst; Franz, Charles M. A. P.; Cousin, Fabien J.; Ross, R. Paul; Hill, Colin

    2016-01-01

    With the emergence of multi-drug resistant bacteria the use of bacteriophages (phages) is gaining renewed interest as promising anti-microbial agents. The aim of this study was to isolate and characterize phages from human fecal samples. Three new coliphages, ɸAPCEc01, ɸAPCEc02 and ɸAPCEc03, were isolated. Their phenotypic and genomic characteristics, and lytic activity against biofilm, and in combination with ciprofloxacin, were investigated. All three phages reduced the growth of E. coli strain DPC6051 at multiplicity of infection (MOI) between 10−3 and 105. A cocktail of all three phages completely inhibited the growth of E. coli. The phage cocktail also reduced biofilm formation and prevented the emergence of phage-resistant mutants which occurred with single phage. When combined with ciprofloxacin, phage alone or in cocktail inhibited the growth of E. coli and prevented the emergence of resistant mutants. These three new phages are promising biocontrol agents for E. coli infections. PMID:27280590

  7. Xanthenedione derivatives, new promising antioxidant and acetylcholinesterase inhibitor agents.

    PubMed

    Seca, Ana M L; Leal, Stephanie B; Pinto, Diana C G A; Barreto, Maria Carmo; Silva, Artur M S

    2014-01-01

    Natural and synthetic xanthone derivatives are well-known for their ability to act as antioxidants and/or enzyme inhibitors. This paper aims to present a successful synthetic methodology towards xanthenedione derivatives and the study of their aromatization to xanthones. Additionally their ability to reduce Fe(III), to scavenge DPPH radicals and to inhibit AChE was evaluated. The results demonstrated that xanthenedione derivative 5e, bearing a catechol unit, showed higher reduction capacity than BHT and similar to quercetin, strong DPPH scavenging activity (EC50 = 3.79 ± 0.06 µM) and it was also showed to be a potent AChEI (IC50 = 31.0 ± 0.09 µM) when compared to galantamine (IC50 = 211.8 ± 9.5 µM). PMID:24950437

  8. A review on promising natural agents effective on hyperlipidemia.

    PubMed

    Bahmani, Mahmoud; Mirhoseini, Mahmoud; Shirzad, Hedayatollah; Sedighi, Mehrnoosh; Shahinfard, Nejmeh; Rafieian-Kopaei, Mahmoud

    2015-07-01

    Hyperlipidemia is a prevalent disease and a major component of the metabolic syndrome resulting from various factors. This disease increases morbidity and mortality when combined with other prevalent diseases such as diabetes mellitus, hypertension, and cardiovascular diseases. The side effects of the current lipid-lowering drugs have increased the tendency to move toward traditional and alternative treatments. Epidemiological observations indicate that using alternative treatments, consumption of medicinal plants, diet, and consumption of fruits have had satisfactory results on the effects of hyperlipidemia in many societies. It should be noted that in majority of societies, even developed countries, the tendency toward eating lipid-lowering medicinal plants has increased extensively. Using these plants especially when common remedies cannot control the disease is significant. Although consumption of medicinal plants by hyperlipidemic patients may show improvement in disease state, drug interaction and side effects may cause complications in disease control. Therefore, in this review, apart from introducing some of the reliable plants effective in inhibition and decrease of hyperlipidemia, the possibility of their intoxication and drug interaction is also presented. PMID:25633423

  9. A review on promising natural agents effective on hyperlipidemia.

    PubMed

    Bahmani, Mahmoud; Mirhoseini, Mahmoud; Shirzad, Hedayatollah; Sedighi, Mehrnoosh; Shahinfard, Nejmeh; Rafieian-Kopaei, Mahmoud

    2015-07-01

    Hyperlipidemia is a prevalent disease and a major component of the metabolic syndrome resulting from various factors. This disease increases morbidity and mortality when combined with other prevalent diseases such as diabetes mellitus, hypertension, and cardiovascular diseases. The side effects of the current lipid-lowering drugs have increased the tendency to move toward traditional and alternative treatments. Epidemiological observations indicate that using alternative treatments, consumption of medicinal plants, diet, and consumption of fruits have had satisfactory results on the effects of hyperlipidemia in many societies. It should be noted that in majority of societies, even developed countries, the tendency toward eating lipid-lowering medicinal plants has increased extensively. Using these plants especially when common remedies cannot control the disease is significant. Although consumption of medicinal plants by hyperlipidemic patients may show improvement in disease state, drug interaction and side effects may cause complications in disease control. Therefore, in this review, apart from introducing some of the reliable plants effective in inhibition and decrease of hyperlipidemia, the possibility of their intoxication and drug interaction is also presented.

  10. New trimethyl chitosan-based composite nanoparticles as promising antibacterial agents.

    PubMed

    El-Sherbiny, Ibrahim; Salih, Ehab; Reicha, Fikry

    2016-01-01

    In the present study, densely dispersed silver nanoparticles (Ag NPs) were rapidly green synthesized in the presence of Rumex dentatus aqueous extract, followed by UV-irradiation reduction. The Ag NPs were characterized using UV-vis spectroscopy, FTIR, XRD, and TEM. Then, the Ag NPs were incorporated into interpenetrating polymeric networks based on cationic trimethyl chitosan (TMCS) and anionic poly(acrylamide-co-sodium acrylate) copolymer to develop a new series of composite nanoparticles as potential antibacterial agents. Both TMCS and poly(acrylamide-co-sodium acrylate) were prepared in the study, and characterized using FTIR, DSC, and SEM. The synthesized Ag NPs showed high purity and uniform particle size distribution with particle size ranged between 5 and 30 nm. The composite nanoparticles demonstrated homogeneous spherical shape with size in the range of 378-402 nm. Both Ag NPs and the composite nanoparticles showed promising bactericidal activity as compared with the control. Moreover, the antibacterial activity of the composite nanoparticles increased along with increasing the concentrations of Ag NPs and the TMCS. PMID:26289003

  11. Amphipathic tail-anchoring peptide is a promising therapeutic agent for prostate cancer treatment

    PubMed Central

    De, Gejing; Ko, Jae-Kyun; Tan, Tao; Zhu, Hua; Li, Haichang; Ma, Jianjie

    2014-01-01

    Amphipathic tail-anchoring peptide (ATAP) derived from the human anti-apoptotic protein Bfl-1 is a potent inducer of apoptosis by targeting mitochondria permeability transition. By linking ATAP to an internalizing RGD peptide (iRGD), selective targeting for ATAP to tumor cell was achieved. Confocal fluorescence microscopy showed that ATAP-iRGD could penetrate into cancer cells and distribute along the mitochondria network. ATAP-iRGD triggered mitochondria-dependent cell death through release of cytochrome c. In an effort to promote ATAP-iRGD physiochemical properties to approach clinic application, amino acid substitution and chemical modification were made with ATAP-iRGD to improve its bioactivity. One of these modified peptides, ATAP-iRGD-M8, was with improved stability and aqueous solubility without compromising in vitro cytotoxicity in cultured cancer cells. In vivo xenograft studies with multiple prostate cancer cell lines showed that intravenous administration of ATAP-iRGD-M8 suppressed tumor growth. Toxicological studies revealed that repetitive intravenous administration of ATAP-iRGD-M8 did not produce significant toxicity in the SV129 mice. Our data suggest that ATAP-iRGD-M8 is a promising agent with high selectivity and limited systemic toxicity for prostate cancer treatment. PMID:25245280

  12. PEPTIDE INHIBITORS OF MK2 SHOW PROMISE FOR INHIBITION OF ABDOMINAL ADHESIONS

    PubMed Central

    Ward, Brian C.; Kavalukas, Sandra; Brugnano, Jamie; Barbul, Adrian; Panitch, Alyssa

    2011-01-01

    Background Abdominal adhesions are a common side effect of surgical procedures with complications including infertility, chronic pain, and bowel obstruction, which may lead to the need for surgical lyses of the adhesions. Mitogen-activated protein kinase-activated protein kinase 2 (MK2) has been implicated in several diseases involving inflammation and fibrosis. Thus, the development of a cell-penetrating peptide (CPP) that modulates MK2 activity may confer therapeutic benefit after abdominal surgery in general and more specifically after bowel anastomosis. Study Design This study evaluated the function of a CPP inhibitor of MK2 in human mesothelial cells and in a rat bowel anastomosis model. To determine IC50 and basic specificity, kinase inhibition was performed using a radiometric assay. Enzyme-Linked Immunoassay (ELISA) was used to evaluate interleukin-6 (IL-6) expression in response to IL-1β and tumor necrosis factor-α (TNF-α) stimulation in vitro to validate MK2 kinase inhibition. Following bowel anastomosis (10 rats for each control and treatment at 4 and 10 days), the rats were evaluated for weight loss, normal healing (colonic burst strength and hydroxyproline content at the anastomosis), and number and density of adhesions. Results The IC50 of the MK2 inhibitor peptide (22µM) was similar to that of the nonspecific small molecule Rottlerin (IC50=5µM). The MK2 inhibitor peptide was effective at suppressing IL-1β and TNF-α stimulated IL-6 expression in mesothelial cells. In vivo, the MK2 inhibitor peptide was effective as suppressing both the density and number of adhesions formed as a result of bowel anastomosis. Importantly, the peptide had no negative effect on normal healing. Conclusions In conclusion, the peptide inhibitor of MK2, MMI-0100, has the potential to significantly reduce inflammation through suppression of inflammatory cytokine expression and showed promise as a therapeutic for abdominal adhesions. PMID:21492875

  13. Occupational Outlook and Projections: Bureau of Labor Statistics Explains Which Jobs Show Promise for 1985

    ERIC Educational Resources Information Center

    La Luz, 1977

    1977-01-01

    The Bureau of Labor Statistics examines job prospects in hundreds of occupations and publishes many books and pamphlets that explain which jobs will and will not be promising between now and 1985, i.e., the Occupational Outlook Handbook and the Occupational Outlook for College Graduates. (NQ)

  14. Consistent Estimates of Tsunami Energy Show Promise for Improved Early Warning

    NASA Astrophysics Data System (ADS)

    Titov, V.; Song, Y. Tony; Tang, L.; Bernard, E. N.; Bar-Sever, Y.; Wei, Y.

    2016-05-01

    Early tsunami warning critically hinges on rapid determination of the tsunami hazard potential in real-time, before waves inundate critical coastlines. Tsunami energy can quickly characterize the destructive potential of generated waves. Traditional seismic analysis is inadequate to accurately predict a tsunami's energy. Recently, two independent approaches have been proposed to determine tsunami source energy: one inverted from the Deep-ocean Assessment and Reporting of Tsunamis (DART) data during the tsunami propagation, and the other derived from the land-based coastal global positioning system (GPS) during tsunami generation. Here, we focus on assessing these two approaches with data from the March 11, 2011 Japanese tsunami. While the GPS approach takes into consideration the dynamic earthquake process, the DART inversion approach provides the actual tsunami energy estimation of the propagating tsunami waves; both approaches lead to consistent energy scales for previously studied tsunamis. Encouraged by these promising results, we examined a real-time approach to determine tsunami source energy by combining these two methods: first, determine the tsunami source from the globally expanding GPS network immediately after an earthquake for near-field early warnings; and then to refine the tsunami energy estimate from nearby DART measurements for improving forecast accuracy and early cancelations. The combination of these two real-time networks may offer an appealing opportunity for: early determination of the tsunami threat for the purpose of saving more lives, and early cancelation of tsunami warnings to avoid unnecessary false alarms.

  15. Innovations at Miami practice show promise for treating high-risk Medicare patients.

    PubMed

    Tanio, Craig; Chen, Christopher

    2013-06-01

    Patients with five or more chronic conditions drive most Medicare costs. Our organization, ChenMed, developed a scalable primary care-led delivery model that focuses on this population while getting reimbursed through full-risk capitation by Medicare Advantage plans. ChenMed is a primary care-led group practice based in Florida that serves low-to-moderate-income elderly patients, largely through the Medicare Advantage program. Our model includes a number of innovations: a one-stop-shop approach for delivering multispecialty services in the community, smaller physician panel sizes of 350-450 patients that allow for intensive health coaching and preventive care, on-site physician pharmacy dispensing, a collaborative physician culture with peer review, and customized information technology. These innovations have improved patient medication adherence, increased the time doctors and patients spend together, and led to high rates of patient satisfaction. Additionally, our Medicare patients have substantially lower rates of hospital use than their peers in the Miami Medicare market. Creating chronic disease centers focused on seniors with multiple chronic conditions is a promising delivery system innovation with major potential to improve the cost and quality of care.

  16. Design or screening of drugs for the treatment of Chagas disease: what shows the most promise?

    PubMed Central

    Lepesheva, Galina I.

    2013-01-01

    Introduction Endemic in Latin America, Chagas disease is now becoming a serious global health problem, and yet has no financial viability for the pharmaceutical industry and remains incurable. In 2012, two antimycotic drugs inhibitors of fungal sterol 14α-demethylase (CYP51) – posaconazole and ravuconazole – entered clinical trials. Availability of the X-ray structure of the orthologous enzyme from the causative agent of the disease, protozoan parasite Trypanosoma cruzi, determined in complexes with posaconazole as well as with several experimental protozoa-specific CYP51 inhibitors opens an excellent opportunity to improve the situation. Areas covered This article summarizes the information available in PubMed and Google on the outcomes of treatment of the chronic Chagas disease. It also outlines the major features of the T. cruzi CYP51 structure and the possible structure-based strategies for rational design of novel T. cruzi specific drugs. Expert opinion There is no doubt that screenings for alternative drug-like molecules as well as mining the T. cruzi genome for novel drug targets are of great value and might eventually lead to groundbreaking discoveries. However, all newly identified molecules must proceed through the long, expensive and low-yielding drug optimization process, and all novel potential drug targets must be validated in terms of their essentiality and druggability. CYP51 is already a well-validated and highly successful target for clinical and agricultural antifungals. With minimal investments into the final stages of their development/trials, T. cruzi-specific CYP51 inhibitors can provide an immediate treatment for Chagas disease, either on their own or in combination with the currently available drugs. PMID:24079515

  17. R&D Project on Algebra Software Seen to Show Promise

    ERIC Educational Resources Information Center

    Trotter, Andrew

    2007-01-01

    Computer software that shows students visual models of mathematical concepts--and lets them manipulate those models by doing math--has a certain intuitive appeal. Now, recent research on SimCalc Mathworlds, one of the pioneering examples of such software, is providing some of the best evidence so far that the approach can lead to gains in student…

  18. Stem cells show promising results for lymphoedema treatment--a literature review.

    PubMed

    Toyserkani, Navid Mohamadpour; Christensen, Marlene Louise; Sheikh, Søren Paludan; Sørensen, Jens Ahm

    2015-04-01

    Lymphoedema is a debilitating condition, manifesting in excess lymphatic fluid and swelling of subcutaneous tissues. Lymphoedema is as of yet still an incurable condition and current treatment modalities are not satisfactory. The capacity of mesenchymal stem cells to promote angiogenesis, secrete growth factors, regulate the inflammatory process, and differentiate into multiple cell types make them a potential ideal therapy for lymphoedema. Adipose tissue is the richest and most accessible source of mesenchymal stem cells and they can be harvested, isolated, and used for therapy in a single stage procedure as an autologous treatment. The aim of this paper was to review all studies using mesenchymal stem cells for lymphoedema treatment with a special focus on the potential use of adipose-derived stem cells. A systematic search was performed and five preclinical and two clinical studies were found. Different stem cell sources and lymphoedema models were used in the described studies. Most studies showed a decrease in lymphoedema and an increased lymphangiogenesis when treated with stem cells and this treatment modality has so far shown great potential. The present studies are, however, subject to bias and more preclinical studies and large-scale high quality clinical trials are needed to show if this emerging therapy can satisfy expectations.

  19. Particulate Titanium Matrix Composites Tested--Show Promise for Space Propulsion Applications

    NASA Technical Reports Server (NTRS)

    Lerch, Bradley A.; Ellis, J. Rodney; Arnold. Steven M.

    2004-01-01

    Uniformly distributed particle-strengthened titanium matrix composites (TMCs) can be manufactured at lower cost than many types of continuous-fiber composites. The innovative manufacturing technology combines cold and hot isostatic pressing procedures to produce near-final-shape components. Material stiffness is increased up to 26-percent greater than that of components made with conventional titanium materials at no significant increase in the weight. The improved mechanical performance and low-cost manufacturing capability motivated an independent review to assess the improved properties of ceramic titanium carbide (TiC) particulate-reinforced titanium at elevated temperature. Researchers at the NASA Glenn Research Center creatively designed and executed deformation and durability tests to reveal operating regimes where these materials could lower the cost and weight of space propulsion systems. The program compares the elevated-temperature performance of titanium alloy Ti-6Al-4V matrix material to an alloy containing 10 wt% of TiC particles. Initial experiments showed that at these relatively low particle concentrations the material stiffness of the TMC was improved 20 percent over that of the plain Ti-6Al-4V alloy when tested at 427 C. The proportional limit and ultimate strength of the composite in tension are 21- and 14-percent greater than those of the plain alloy. Compression tests showed that the proportional limit is about 30 percent greater for TMC than for the plain alloy. The enhanced deformation resistance of the TMC was also evident in a series of tensile and compressive stress relaxation tests that were made. Specimens were subjected to tensile or compressive strain amplitudes of 0.75 percent for 24 hr followed by a return to zero strain imposed for 24 hr. The stress relaxation data were normalized with respect to the maximum stress for each case and plotted as a function of time in the following graph. Tensile stresses relaxed 19 percent for the

  20. The biodistribution of self-assembling protein nanoparticles shows they are promising vaccine platforms

    PubMed Central

    2013-01-01

    Background Because of the need to limit side-effects, nanoparticles are increasingly being studied as drug-carrying and targeting tools. We have previously reported on a scheme to produce protein-based self-assembling nanoparticles that can act as antigen display platforms. Here we attempted to use the same system for cancer-targeting, making use of a C-terminal bombesin peptide that has high affinity for a receptor known to be overexpressed in certain tumors, as well as an N-terminal polyhistidine tag that can be used for radiolabeling with technetium tricarbonyl. Results In order to increase circulation time, we experimented with PEGylated and unPEGylated varities typo particle. We also tested the effect of incorporating different numbers of bombesins per nanoparticle. Biophysical characterization determined that all configurations assemble into regular particles with relatively monodisperse size distributions, having peaks of about 33 – 36 nm. The carbonyl method used for labeling produced approximately 80% labeled nanoparticles. In vitro, the nanoparticles showed high binding, both specific and non-specific, to PC-3 prostate cancer cells. In vivo, high uptake was observed for all nanoparticle types in the spleens of CD-1 nu/nu mice, decreasing significantly over the course of 24 hours. High uptake was also observed in the liver, while only low uptake was seen in both the pancreas and a tumor xenograft. Conclusions The data suggest that the nanoparticles are non-specifically taken up by the reticuloendothelial system. Low uptake in the pancreas and tumor indicate that there is little or no specific targeting. PEGylation or increasing the amount of bombesins per nanoparticle did not significantly improve targeting. In particular, the uptake in the spleen, which is a primary organ of the immune system, highlights the potential of the nanoparticles as vaccine carriers. Also, the decrease in liver and spleen radioactivity with time implies that the nanoparticles

  1. Substituted benzenediol Schiff bases as promising new anti-glycation agents.

    PubMed

    Choudhary, M Iqbal; Abbas, Ghulam; Ali, Saqib; Shuja, Shaukat; Khalid, Nasir; Khan, Khalid M; Atta-ur-Rahman; Basha, Fatima Z

    2011-02-01

    A feature of diabetes is that the rate of protein glycation and the formation of advanced glycation endproducts (AGEs) increases spontaneously due to the abnormally elevated levels of sugar in the blood. The glycation of proteins is associated with a large number of late diabetic complications (retinopathy, neuropathy, atherosclerosis, end stage renal diseases, rheumatoid arthritis and neurodegenerative diseases). The increase in diabetic complications is a major cause of morbidity and mortality, which has increased significantly in the last two decades. Therefore, there is a considerable recent interest in the identification of lead molecules, which can inhibit the glycation process or slow it down considerably. A new class of anti-glycation agents has been identified, based on the spectrofluorimetric analysis of fluorescent advanced glycation endproducts (AGEs), benzenediol Schiff bases, and their structure-activity relationships have been studied. Some of these compounds have shown a promising anti-glycation potential in vitro. PMID:20583858

  2. Farther, Faster: Six Promising Programs Show How Career Pathway Bridges Help Basic Skills Students Earn Credentials That Matter

    ERIC Educational Resources Information Center

    Strawn, Julie

    2011-01-01

    Students forced to complete a long sequence of remedial or English language classes before they can begin their postsecondary program rarely earn college certificates or degrees. This brief highlights six promising programs that show how career pathway bridges help lower-skilled students move farther and faster along college and career paths…

  3. Effect of tungsten concentration on growth of acetobacter xylinum as a promising agent for eco-friendly recycling system

    NASA Astrophysics Data System (ADS)

    Nandiyanto, A. B. D.; Halimatul, H. S.; Rosyid, N. H.; Effendi, D. B.

    2016-04-01

    Effect of tungsten (W) concentration on Acetobacter xylinum growth was studied. In the experimental procedure, concentration of W in the bacterial growth medium containing pineapple peels waste was varied from 0.5 to 50 ppm. To confirm the influence of W, the bacterial incubation process was carried out for 72 hours. Spectrophotometer analysis showed that the growth rate of Acetobacter xylinum decreased with increasing concentration of W. The result from fourier transform infra red analysis showed a slightly change on the absorption peak intensities and informing the interaction of W ion and bacteria cell. The result confirmed that Acetobacter xylinum was able to uptake W concentration up to 15 ppm, indicating that Acetobacter xylinum might act as a promising agent for eco-friendly recycling system.

  4. Novel amidines and analogues as promising agents against intracellular parasites: a systematic review.

    PubMed

    Soeiro, M N C; Werbovetz, K; Boykin, D W; Wilson, W D; Wang, M Z; Hemphill, A

    2013-07-01

    Parasitic protozoa comprise diverse aetiological agents responsible for important diseases in humans and animals including sleeping sickness, Chagas disease, leishmaniasis, malaria, toxoplasmosis and others. They are major causes of mortality and morbidity in tropical and subtropical countries, and are also responsible for important economic losses. However, up to now, for most of these parasitic diseases, effective vaccines are lacking and the approved chemotherapeutic compounds present high toxicity, increasing resistance, limited efficacy and require long periods of treatment. Many of these parasitic illnesses predominantly affect low-income populations of developing countries for which new pharmaceutical alternatives are urgently needed. Thus, very low research funding is available. Amidine-containing compounds such as pentamidine are DNA minor groove binders with a broad spectrum of activities against human and veterinary pathogens. Due to their promising microbicidal activity but their rather poor bioavailability and high toxicity, many analogues and derivatives, including pro-drugs, have been synthesized and screened in vitro and in vivo in order to improve their selectivity and pharmacological properties. This review summarizes the knowledge on amidines and analogues with respect to their synthesis, pharmacological profile, mechanistic and biological effects upon a range of intracellular protozoan parasites. The bulk of these data may contribute to the future design and structure optimization of new aromatic dicationic compounds as novel antiparasitic drug candidates.

  5. Novel amidines and analogues as promising agents against intracellular parasites: a systematic review

    PubMed Central

    Soeiro, M. N. C.; Werbovetz, K.; Boykin, D.W.; Wilson, W. D.; Wang, M. Z.; Hemphill, A.

    2013-01-01

    SUMMARY Parasitic protozoa comprise diverse aetiological agents responsible for important diseases in humans and animals including sleeping sickness, Chagas disease, leishmaniasis, malaria, toxoplasmosis and others. They are major causes of mortality and morbidity in tropical and subtropical countries, and are also responsible for important economic losses. However, up to now, for most of these parasitic diseases, effective vaccines are lacking and the approved chemotherapeutic compounds present high toxicity, increasing resistance, limited efficacy and require long periods of treatment. Many of these parasitic illnesses predominantly affect low-income populations of developing countries for which new pharmaceutical alternatives are urgently needed. Thus, very low research funding is available. Amidine-containing compounds such as pentamidine are DNA minor groove binders with a broad spectrum of activities against human and veterinary pathogens. Due to their promising microbicidal activity but their rather poor bioavailability and high toxicity, many analogues and derivatives, including pro-drugs, have been synthesized and screened in vitro and in vivo in order to improve their selectivity and pharmacological properties. This review summarizes the knowledge on amidines and analogues with respect to their synthesis, pharmacological profile, mechanistic and biological effects upon a range of intracellular protozoan parasites. The bulk of these data may contribute to the future design and structure optimization of new aromatic dicationic compounds as novel antiparasitic drug candidates. PMID:23561006

  6. Resveratrol derivatives as promising chemopreventive agents with improved potency and selectivity

    PubMed Central

    Kondratyuk, Tamara P.; Park, Eun-Jung; Marler, Laura E.; Ahn, Soyoun; Yuan, Yang; Choi, Yongsoo; Yu, Rui; van Breemen, Richard B.; Sun, Bin; Hoshino, Juma; Cushman, Mark; Jermihov, Katherine C.; Mesecar, Andrew D.; Grubbs, Clinton J.; Pezzuto, John M.

    2014-01-01

    Despite scores of investigations, the actual impact of resveratrol (3,5,4′-trihydroxy-trans-stilbene) on human health, as a dietary component or supplement, remains moot. This is due to many factors, such as relatively low potency, pleiotropic mechanisms, and rapid metabolism. Nonetheless, as a promiscuous molecule that interacts with numerous targets, resveratrol can be viewed as a scaffold for designing structural relatives potentially capable of mediating more intense responses with greater mechanistic stringency. We currently report the synthesis and biological evaluation of 92 stilbene analogs. The compounds were tested with in vitro assays for activation of quinone reductase 1, inhibition of QR2, nitric oxide production, aromatase, NFκB, TPA-induced ornithine decarboxylase, or cyclooxygenase-1 and -2, quenching of 2,2-diphenyl-1-picrylhydrazyl free radical, interaction with estrogen receptors, and as antiproliferative agents. Several compounds were found to mediate responses with much greater potency than resveratrol; some mediated pleiotropic responses, as is the case with the parent molecule, but others were highly specific or totally inactive. When administered to rats, higher serum concentrations and greater stability was demonstrated with prototype lead molecules. Due to structural simplicity, facile syntheses are available for large-scale production. These data support the promise of more advanced development of novel resveratrol derivatives as drug entities. PMID:21714126

  7. Short AntiMicrobial Peptides (SAMPs) as a class of extraordinary promising therapeutic agents.

    PubMed

    Ramesh, Suhas; Govender, Thavendran; Kruger, Hendrik G; de la Torre, Beatriz G; Albericio, Fernando

    2016-07-01

    The emergence of multidrug resistant bacteria has a direct impact on global public health because of the reduced potency of existing antibiotics against pathogens. Hence, there is a pressing need for new drugs with different modes of action that can kill microorganisms. Antimicrobial peptides (AMPs) can be regarded as an alternative tool for this purpose because they are proven to have therapeutic effects with broad-spectrum activities. There are some hurdles in using AMPs as clinical candidates such as toxicity, lack of stability and high budgets required for manufacturing. This can be overcome by developing shorter and more easily accessible AMPs, the so-called Short AntiMicrobial Peptides (SAMPs) that contain between two and ten amino acid residues. These are emerging as an attractive class of therapeutic agents with high potential for clinical use and possessing multifunctional activities. In this review we attempted to compile those SAMPs that have exhibited biological properties which are believed to hold promise for the future. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27352996

  8. Graphene oxide-silver nanocomposite as a promising biocidal agent against methicillin-resistant Staphylococcus aureus

    PubMed Central

    de Moraes, Ana Carolina Mazarin; Lima, Bruna Araujo; de Faria, Andreia Fonseca; Brocchi, Marcelo; Alves, Oswaldo Luiz

    2015-01-01

    Background Methicillin-resistant Staphylococcus aureus (MRSA) has been responsible for serious hospital infections worldwide. Nanomaterials are an alternative to conventional antibiotic compounds, because bacteria are unlikely to develop microbial resistance against nanomaterials. In the past decade, graphene oxide (GO) has emerged as a material that is often used to support and stabilize silver nanoparticles (AgNPs) for the preparation of novel antibacterial nanocomposites. In this work, we report the synthesis of the graphene-oxide silver nanocomposite (GO-Ag) and its antibacterial activity against relevant microorganisms in medicine. Materials and methods GO-Ag nanocomposite was synthesized through the reduction of silver ions (Ag+) by sodium citrate in an aqueous GO dispersion, and was extensively characterized using ultraviolet-visible absorption spectroscopy, X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, and transmission electron microscopy. The antibacterial activity was evaluated by microdilution assays and time-kill experiments. The morphology of bacterial cells treated with GO-Ag was investigated via transmission electron microscopy. Results AgNPs were well distributed throughout GO sheets, with an average size of 9.4±2.8 nm. The GO-Ag nanocomposite exhibited an excellent antibacterial activity against methicillin-resistant S. aureus, Acinetobacter baumannii, Enterococcus faecalis, and Escherichia coli. All (100%) MRSA cells were inactivated after 4 hours of exposure to GO-Ag sheets. In addition, no toxicity was found for either pristine GO or bare AgNPs within the tested concentration range. Transmission electronic microscopy images offered insights into how GO-Ag nanosheets interacted with bacterial cells. Conclusion Our results indicate that the GO-Ag nanocomposite is a promising antibacterial agent against common nosocomial bacteria, particularly antibiotic-resistant MRSA. Morphological injuries on MRSA cells

  9. Bee Pollen as a Promising Agent in the Burn Wounds Treatment

    PubMed Central

    Olczyk, Paweł; Koprowski, Robert; Kaźmierczak, Justyna; Mencner, Lukasz; Wojtyczka, Robert; Stojko, Jerzy; Olczyk, Krystyna; Komosinska-Vassev, Katarzyna

    2016-01-01

    The aim of the present study was to visualize the benefits and advantages derived from preparations based on extracts of bee pollen as compared to pharmaceuticals commonly used in the treatment of burns. The bee pollen ointment was applied for the first time in topical burn treatment. Experimental burn wounds were inflicted on two white, domestic pigs. Clinical, histopathological, and microbiological assessment of specimens from burn wounds, inflicted on polish domestic pigs, treated with silver sulfadiazine or bee pollen ointment, was done. The comparative material was constituted by either tissues obtained from wounds treated with physiological saline or tissues obtained from wounds which were untreated. Clinical and histopathological evaluation showed that applied apitherapeutic agent reduces the healing time of burn wounds and positively affects the general condition of the animals. Moreover the used natural preparation proved to be highly effective antimicrobial agent, which was reflected in a reduction of the number of microorganisms in quantitative research and bactericidal activity of isolated strains. On the basis of the obtained bacteriological analysis, it may be concluded that the applied bee pollen ointment may affect the wound healing process of burn wounds, preventing infection of the newly formed tissue. PMID:27293466

  10. Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents.

    PubMed

    Abrão, Pedro Henrique O; Pizi, Rafael B; de Souza, Thiago B; Silva, Naiara C; Fregnan, Antonio M; Silva, Fernanda N; Coelho, Luiz Felipe L; Malaquias, Luiz Cosme C; Dias, Amanda Latercia T; Dias, Danielle F; Veloso, Marcia P; Carvalho, Diogo T

    2015-10-01

    New Mannich base-type eugenol derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 4-allyl-2-methoxy-6-(morpholin-4-ylmethyl) phenyl benzoate (7) and 4-{5-allyl-2-[(4-chlorobenzoyl)oxy]-3-methoxybenzyl}morpholin-4-ium chloride (8) were found to be the most effective antifungal compounds with low IC50 values, some of them well below those of reference drug fluconazole. The most significant IC50 values were those of 7 against C. glabrata (1.23 μm), C. albicans and C. krusei (both 0.63 μm). Additionally, the synthesized compounds were evaluated for their in vitro cytotoxic effects on human mononuclear cells. As result, the cytotoxic activity of eugenol in eukaryotic cells decreased with the introduction of the morpholinyl group. Given these findings, we point out compounds 7 and 8 as the most promising derivatives because they showed potency values greater than those of eugenol and fluconazole and they also presented high selectivity indexes.

  11. Developmental Reversals in Risky Decision Making: Intelligence Agents Show Larger Decision Biases Than College Students

    PubMed Central

    Reyna, Valerie F.; Chick, Christina F.; Corbin, Jonathan C.; Hsia, Andrew N.

    2014-01-01

    Intelligence agents make risky decisions routinely, with serious consequences for national security. Although common sense and most theories imply that experienced intelligence professionals should be less prone to irrational inconsistencies than college students, we show the opposite. Moreover, the growth of experience-based intuition predicts this developmental reversal. We presented intelligence agents, college students, and postcollege adults with 30 risky-choice problems in gain and loss frames and then compared the three groups’ decisions. The agents not only exhibited larger framing biases than the students, but also were more confident in their decisions. The postcollege adults (who were selected to be similar to the students) occupied an interesting middle ground, being generally as biased as the students (sometimes more biased) but less biased than the agents. An experimental manipulation testing an explanation for these effects, derived from fuzzy-trace theory, made the students look as biased as the agents. These results show that, although framing biases are irrational (because equivalent outcomes are treated differently), they are the ironical output of cognitively advanced mechanisms of meaning making. PMID:24171931

  12. Developmental reversals in risky decision making: intelligence agents show larger decision biases than college students.

    PubMed

    Reyna, Valerie F; Chick, Christina F; Corbin, Jonathan C; Hsia, Andrew N

    2014-01-01

    Intelligence agents make risky decisions routinely, with serious consequences for national security. Although common sense and most theories imply that experienced intelligence professionals should be less prone to irrational inconsistencies than college students, we show the opposite. Moreover, the growth of experience-based intuition predicts this developmental reversal. We presented intelligence agents, college students, and postcollege adults with 30 risky-choice problems in gain and loss frames and then compared the three groups' decisions. The agents not only exhibited larger framing biases than the students, but also were more confident in their decisions. The postcollege adults (who were selected to be similar to the students) occupied an interesting middle ground, being generally as biased as the students (sometimes more biased) but less biased than the agents. An experimental manipulation testing an explanation for these effects, derived from fuzzy-trace theory, made the students look as biased as the agents. These results show that, although framing biases are irrational (because equivalent outcomes are treated differently), they are the ironical output of cognitively advanced mechanisms of meaning making. PMID:24171931

  13. Macromolecular Imaging Agents Containing Lanthanides: Can Conceptual Promise Lead to Clinical Potential?

    PubMed Central

    Bryson, Joshua; Reineke, Jeffrey W.; Reineke, Theresa M.

    2012-01-01

    Macromolecular magnetic resonance imaging (MRI) contrast agents are increasingly being used to improve the resolution of this noninvasive diagnostic technique. All clinically-approved T1 contrast agents are small molecule chelates of gadolinium [Gd(III)] that affect bound water proton relaxivity. Both the small size and monomeric nature of these agents ultimately limits the image resolution enhancement that can be achieved for both contrast enhancement and pharmacokinetic/biodistribution reasons. The multimeric nature of macromolecules, such as polymers, dendrimers, and noncovalent complexes of small molecule agents with proteins, have been shown to significantly increase the image contrast and resolution due to their large size and ability to incorporate multiple Gd(III) chlelation sites. Also, macromolecular agents are advantageous as they have the ability to be designed to be nontoxic, hydrophilic, easily purified, aggregation-resistant, and have controllable three-dimensional macromolecular structure housing the multiple lanthanide chelation sites. For these reasons, large molecule diagnostics have the ability to significantly increase the relaxivity of water protons within the targeted tissues and thus the image resolution for many diagnostic applications. The FDA approval of a contrast agent that consists of a reversible, non-covalent coupling of a small Gd(III) chelate with serum albumin for blood pool imaging (marketed under the trade names of Vasovist and Ablivar) proved to be one of the first diagnostic agent to capitalize on these benefits from macromolecular association in humans. However, much research and development is necessary to optimize the safety of these unique agents for in vivo use and potential clinical development. To this end, recent work in the field of polymer, dendrimer, and noncovalent complex-based imaging agents are reviewed herein and the future outlook of this field is discussed. PMID:23467737

  14. In vitro evaluation of (-)α-bisabolol as a promising agent against Leishmania amazonensis.

    PubMed

    Rottini, Mariana Margatto; Amaral, Ana Claudia Fernandes; Ferreira, Jose Luiz Pinto; Silva, Jefferson Rocha de Andrade; Taniwaki, Noemi Nosomi; Souza, Celeste da Silva Freitas de; d'Escoffier, Luiz Ney; Almeida-Souza, Fernando; Hardoim, Daiana de Jesus; Gonçalves da Costa, Sylvio Celso; Calabrese, Kátia da Silva

    2015-01-01

    Current treatments for leishmaniasis present some difficulties due to their toxicity, the use of the intravenous route for administration and therapy duration, which may lead to treatment discontinuation. The aim of this study is to investigate new treatment alternatives to improve patients well being. Therefore, we evaluated the inhibitory effect of (-)α-bisabolol, a sesquiterpene alcohol found in various essential oils of different plant species, against the promastigotes and intracellular amastigotes forms of Leishmania amazonensis, as well as the cytotoxic, morphological and ultrastructural alterations of treated cells. Promastigotes forms of L. amazonensis were incubated with (-)α-bisabolol to determine the antileishmanial activity of this compound. The cytotoxicity effect was evaluated by testing against J774.G8 cells. After these tests, the infected and uninfected cells with L. amazonensis were used to determine if the (-)α-bisabolol was able to kill intracellular parasites and to cause some morphological changes in the cells. The (-)α-bisabolol compound showed significant antileishmanial activity against promastigotes with a 50% effective concentration of 8.07 µg/ml (24 h) and 4.26 µg/ml (48 h). Against intracellular amastigotes the IC50 (inhibitory concentration) of (-)α-bisabolol (24 h) was 4.15 µg/ml. The (-)α-bisabolol also showed a cytotoxic effect against the macrophage strain J774.G8. The value of 50% cytotoxic concentration was 14.82 µg/ml showing that (-)α-bisabolol is less toxic to macrophages than to the parasite. Ultrastructural studies of treated promastigotes and amastigotes showed several alterations, such as loss of cytoplasmic organelles, including the nucleus, and the presence of lipid inclusions. This study showed that (-)α-bisabolol has promising antileishmanial properties, as it can act against the promastigote forms and is able to penetrate the cell, and is also active against the amastigote forms. About 69

  15. Benzofuran as a promising scaffold for the synthesis of antimicrobial and antibreast cancer agents: A review

    PubMed Central

    Khodarahmi, Ghadamali; Asadi, Parvin; Hassanzadeh, Farshid; Khodarahmi, Elham

    2015-01-01

    Benzofuran as an important heterocyclic compound is extensively found in natural products as well as synthetic materials. Since benzofuran drivatives display a diverse array of pharmacological activities, an interest in developing new biologically active agents from benzofuran is still under consideration. This review highlights recent findings on biological activities of benzofuran derivatives as antimicrobial and antibreast cancer agents and lays emphasis on the importance of benzofurans as a major source for drug design and development. PMID:26941815

  16. Olive Oil Phenols as Promising Multi-targeting Agents Against Alzheimer's Disease.

    PubMed

    Rigacci, Stefania

    2015-01-01

    Amyloid diseases are characterized by the deposition of typically aggregated proteins/peptides in tissues, associated with degeneration and progressive functional impairment. Alzheimer's disease is one of the most studied neurodegenerative amyloid diseases and, in Western countries, a significant cause of dementia in the elderly. The so-called "Mediterranean diet" has been considered for long as the healthier dietary regimen, characterised by a great abundance in vegetables and fruits, extra virgin olive oil as the main source of fat, a moderate consumption of red wine and a reduced intake of proteins from red meat. Recent epidemiological studies support the efficacy of the Mediterranean diet not only against cardiovascular and cancer diseases (as previously demonstrated) but also against the cognitive decline associated with ageing, and several data are highlighting the role played by natural phenols, of which red wine and extra virgin olive oil are rich, in such context. In the meantime, studies conducted both in vivo and in vitro have started to reveal the great potential of the phenolic component of extra virgin olive oil (mainly oleuropein aglycone and oleocanthal) in counteracting amyloid aggregation and toxicity, with a particular emphasis on the pathways involved in the onset and progression of Alzheimer's disease: amyloid precursor protein processing, amyloid-beta (Aβ) peptide and tau aggregation, autophagy impairment, neuroinflammation. The aim of this review is to summarize the results of such research efforts, showing how the action of these phenols goes far beyond their renowned antioxidant activity and revealing their potential as multi-targeting agents against Alzheimer's disease. PMID:26092624

  17. Olive Oil Phenols as Promising Multi-targeting Agents Against Alzheimer's Disease.

    PubMed

    Rigacci, Stefania

    2015-01-01

    Amyloid diseases are characterized by the deposition of typically aggregated proteins/peptides in tissues, associated with degeneration and progressive functional impairment. Alzheimer's disease is one of the most studied neurodegenerative amyloid diseases and, in Western countries, a significant cause of dementia in the elderly. The so-called "Mediterranean diet" has been considered for long as the healthier dietary regimen, characterised by a great abundance in vegetables and fruits, extra virgin olive oil as the main source of fat, a moderate consumption of red wine and a reduced intake of proteins from red meat. Recent epidemiological studies support the efficacy of the Mediterranean diet not only against cardiovascular and cancer diseases (as previously demonstrated) but also against the cognitive decline associated with ageing, and several data are highlighting the role played by natural phenols, of which red wine and extra virgin olive oil are rich, in such context. In the meantime, studies conducted both in vivo and in vitro have started to reveal the great potential of the phenolic component of extra virgin olive oil (mainly oleuropein aglycone and oleocanthal) in counteracting amyloid aggregation and toxicity, with a particular emphasis on the pathways involved in the onset and progression of Alzheimer's disease: amyloid precursor protein processing, amyloid-beta (Aβ) peptide and tau aggregation, autophagy impairment, neuroinflammation. The aim of this review is to summarize the results of such research efforts, showing how the action of these phenols goes far beyond their renowned antioxidant activity and revealing their potential as multi-targeting agents against Alzheimer's disease.

  18. Agent-based modeling of the immune system: NetLogo, a promising framework.

    PubMed

    Chiacchio, Ferdinando; Pennisi, Marzio; Russo, Giulia; Motta, Santo; Pappalardo, Francesco

    2014-01-01

    Several components that interact with each other to evolve a complex, and, in some cases, unexpected behavior, represents one of the main and fascinating features of the mammalian immune system. Agent-based modeling and cellular automata belong to a class of discrete mathematical approaches in which entities (agents) sense local information and undertake actions over time according to predefined rules. The strength of this approach is characterized by the appearance of a global behavior that emerges from interactions among agents. This behavior is unpredictable, as it does not follow linear rules. There are a lot of works that investigates the immune system with agent-based modeling and cellular automata. They have shown the ability to see clearly and intuitively into the nature of immunological processes. NetLogo is a multiagent programming language and modeling environment for simulating complex phenomena. It is designed for both research and education and is used across a wide range of disciplines and education levels. In this paper, we summarize NetLogo applications to immunology and, particularly, how this framework can help in the development and formulation of hypotheses that might drive further experimental investigations of disease mechanisms. PMID:24864263

  19. Agent-Based Modeling of the Immune System: NetLogo, a Promising Framework

    PubMed Central

    Chiacchio, Ferdinando; Russo, Giulia; Pappalardo, Francesco

    2014-01-01

    Several components that interact with each other to evolve a complex, and, in some cases, unexpected behavior, represents one of the main and fascinating features of the mammalian immune system. Agent-based modeling and cellular automata belong to a class of discrete mathematical approaches in which entities (agents) sense local information and undertake actions over time according to predefined rules. The strength of this approach is characterized by the appearance of a global behavior that emerges from interactions among agents. This behavior is unpredictable, as it does not follow linear rules. There are a lot of works that investigates the immune system with agent-based modeling and cellular automata. They have shown the ability to see clearly and intuitively into the nature of immunological processes. NetLogo is a multiagent programming language and modeling environment for simulating complex phenomena. It is designed for both research and education and is used across a wide range of disciplines and education levels. In this paper, we summarize NetLogo applications to immunology and, particularly, how this framework can help in the development and formulation of hypotheses that might drive further experimental investigations of disease mechanisms. PMID:24864263

  20. Agent-based modeling of the immune system: NetLogo, a promising framework.

    PubMed

    Chiacchio, Ferdinando; Pennisi, Marzio; Russo, Giulia; Motta, Santo; Pappalardo, Francesco

    2014-01-01

    Several components that interact with each other to evolve a complex, and, in some cases, unexpected behavior, represents one of the main and fascinating features of the mammalian immune system. Agent-based modeling and cellular automata belong to a class of discrete mathematical approaches in which entities (agents) sense local information and undertake actions over time according to predefined rules. The strength of this approach is characterized by the appearance of a global behavior that emerges from interactions among agents. This behavior is unpredictable, as it does not follow linear rules. There are a lot of works that investigates the immune system with agent-based modeling and cellular automata. They have shown the ability to see clearly and intuitively into the nature of immunological processes. NetLogo is a multiagent programming language and modeling environment for simulating complex phenomena. It is designed for both research and education and is used across a wide range of disciplines and education levels. In this paper, we summarize NetLogo applications to immunology and, particularly, how this framework can help in the development and formulation of hypotheses that might drive further experimental investigations of disease mechanisms.

  1. Zampanolide and dactylolide: cytotoxic tubulin-assembly agents and promising anticancer leads

    PubMed Central

    2014-01-01

    Covering: through January 2014 Zampanolide is a marine natural macrolide and a recent addition to the family of microtubule-stabilizing cytotoxic agents. Zampanolide exhibits unique effects on tubulin assembly and is more potent than paclitaxel against several multi-drug resistant cancer cell lines. A high-resolution crystal structure of αβ-tubulin in complex with zampanolide explains how taxane-site microtubule-stabilizing agents promote microtubule assemble and stability. This review provides an overview of current developments of zampanolide and its related but less potent analogue dactylolide, covering their natural sources and isolation, structure and conformation, cytotoxic potential, structure–activity studies, mechanism of action, and syntheses. PMID:24945566

  2. Recent advances in ytterbium-based contrast agents for in vivo X-ray computed tomography imaging: promises and prospects.

    PubMed

    Liu, Yanlan; Liu, Jianhua; Ai, Kelong; Yuan, Qinghai; Lu, Lehui

    2014-01-01

    X-ray computed tomography (CT) imaging is one of the most widely used diagnostic imaging techniques in the clinic, and has raised significant interest in recent years both in research and practice owing to its many advantages such as deep penetration depth, high resolution and facile image processing. Developing heavy metal-based CT contrast agents, especially heavy metal-containing nanoparticulate CT contrast agents, has become a key focus in research fields to address issues of clinical iodinated agents involving short circulation time, low contrast efficiency and potential renal toxicity. In this review, we summarize the development of ytterbium (Yb)-based CT contrast agents and highlight the design and applications of Yb-based nanoparticulate CT contrast agents. Yb has high atomic number and higher abundance in the earth's crust relative to Au, Ta and Bi, which have received much attention as a CT contrast agents. In particular, in contrast to these metal elements, as well as I, Yb has K-edge energy that is located just within the higher-intensity region of X-ray spectra, which can induce significant enhancement in the contrast efficiency. When encapsulated in nanoparticles, Yb can remain in the circulation for a long time. This long in vivo circulation time, combined with the proper K-edge energy and a large absorption cross-section of Yb in the near-infrared region, makes Yb-based nanoparticles particularly promising in angiography, 'multicolor' spectral CT imaging, and multimodal imaging. Finally, we also discuss the prospects and the challenges in the development of Yb-based CT contrast agents.

  3. Terpinen-4-ol: A Novel and Promising Therapeutic Agent for Human Gastrointestinal Cancers

    PubMed Central

    Shapira, Shiran; Pleban, Shlomo; Kazanov, Diana; Tirosh, Peter; Arber, Nadir

    2016-01-01

    Background Terpinen-4-ol, a naturally occurring monoterpene is the main bioactive component of tea-tree oil and has been shown to have many biological activities. Aim To study the antitumor effects of terpinen-4-ol and its mechanism of action in prostate and GI malignancies, alone and in combination with chemotherapeutic and biological agents. Methods Terpinen-4-ol was administrated alone or combined with standard chemotherapy (Oxaliplatin, Fluorouracil, Gemcitabine, Tarceva) and biological agent (Cetuximab). It was also combined with humanized anti-CD24 mAbs (was developed by us). Killing effects were measured qualitatively by light microscopy and quantitatively using the MTT and FACS analysis, following treatment of colorectal, pancreatic, gastric and prostate cancer cells. Terpinen-4-ol effect on tumor development was evaluated in xenograft model. Results Terpinen-4-ol induces a significant growth inhibition of colorectal, pancreatic, prostate and gastric cancer cells in a dose-dependent manner (10–90% in 0.005–0.1%). Terpinen-4-ol and various anti-cancer agents (0.2μM oxaliplatin and 0.5μM fluorouracil) demonstrated a synergistic inhibitory effect (83% and 91%, respectively) on cancer cell proliferation. In KRAS mutated colorectal cancer cells, which are resistant to anti-EGFR therapy, combining of terpinen-4-ol with cetuximab (1 μM) resulted in impressive efficacy of 80–90% growth inhibition. Sub-toxic concentrations of terpinen-4-ol potentiate anti-CD24 mAb (150μg/ml)-induced growth inhibition (90%). Considerable reduction in tumor volume was seen following terpinen-4-ol (0.2%) treatment alone and with cetuximab (10mg/kg) (40% and 63%, respectively) as compare to the control group. Conclusion Terpinen-4-ol significantly enhances the effect of several chemotherapeutic and biological agents. The possible molecular mechanism for its activity involves induction of cell-death rendering this compound as a potential anti-cancer drug alone and in

  4. Honokiol: a promising small molecular weight natural agent for the growth inhibition of oral squamous cell carcinoma cells.

    PubMed

    Chen, Xi-Rui; Lu, Rui; Dan, Hong-Xia; Liao, Ga; Zhou, Min; Li, Xiao-Yu; Ji, Ning

    2011-01-01

    Honokiol (HNK) is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma (OSCC) cells is unknown. We investigated the antitumor activities of HNK on OSCC cells in vitro for the first time. The inhibitory effects of HNK on the growth and proliferation of OSCC cells were demonstrated via in vitro 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and propidium iodide (PI) assays, and the apoptotic cells were investigated by the observation of morphological changes and detection of DNA fragmentation via PI, TdT-mediated dUTP-biotin nick end labeling (TUNEL), and DNA ladder assays, as well as flow cytometry assay. The results showed that HNK inhibited the growth and proliferation of OSCC cells in vitro in a time and dose-dependent manner. The inhibitory effect was associated with the cell apoptosis induced by HNK, evidenced by the morphological features of apoptotic cells, TUNEL-positive cells and a degradation of chromosomal DNA into small internucleosomal fragments. The study also demonstrated here that the inhibition or apoptosis mediated by 15 microg x mL(-1) or 20 microg x mL(-1) of HNK were more stronger compared with those of 20 microg x mL(-1) 5-fluorouracil (5-Fu, the control) applied to OSCC cells, when the ratio of OSCC cell numbers were measured between the treatment of different concentrations of HNK to the 5-Fu treatment for 48 h. HNK is a promising compound that can be potentially used as a novel treatment agent for human OSCC. PMID:21449214

  5. Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer's disease.

    PubMed

    González-Naranjo, Pedro; Pérez-Macias, Natalia; Campillo, Nuria E; Pérez, Concepción; Arán, Vicente J; Girón, Rocio; Sánchez-Robles, Eva; Martín, María Isabel; Gómez-Cañas, María; García-Arencibia, Moisés; Fernández-Ruiz, Javier; Páez, Juan A

    2014-02-12

    Designing drugs with a specific multi-target profile is a promising approach against multifactorial illnesses as Alzheimer's disease. In this work, new indazole ethers that possess dual activity as both cannabinoid agonists CB2 and inhibitors of BuChE have been designed by computational methods. On the basis of this knowledge, the synthesis, pharmacological evaluation and docking studies of a new class of indazoles has been performed. Pharmacological evaluation includes radioligand binding assays with [(3)H]-CP55940 for CB1R and CB2R and functional activity for cannabinoid receptors on isolated tissue. Additionally, in vitro inhibitory assays of AChE/BuChE and the corresponding competition studies have been carried out. The results of pharmacological tests have revealed that three of these derivatives behave as CB2 cannabinoid agonists and simultaneously show BuChE inhibition. In particular, compounds 3 and 24 have emerged as promising candidates as novel cannabinoids that inhibit BuChE by a non-competitive or mixed mechanism, respectively. On the other hand, both molecules show antioxidant properties. PMID:24378710

  6. Complex of C60 Fullerene with Doxorubicin as a Promising Agent in Antitumor Therapy

    NASA Astrophysics Data System (ADS)

    Prylutska, Svitlana V.; Skivka, Larysa M.; Didenko, Gennadiy V.; Prylutskyy, Yuriy I.; Evstigneev, Maxim P.; Potebnya, Grygoriy P.; Panchuk, Rostyslav R.; Stoika, Rostyslav S.; Ritter, Uwe; Scharff, Peter

    2015-12-01

    The main aim of this work was to evaluate the effect of doxorubicin in complex with C60 fullerene (C60 + Dox) on the growth and metastasis of Lewis lung carcinoma in mice and to perform a primary screening of the potential mechanisms of C60 + Dox complex action. We found that volume of tumor from mice treated with the C60 + Dox complex was 1.4 times less than that in control untreated animals. The number of metastatic foci in lungs of animals treated with C60 + Dox complex was two times less than that in control untreated animals. Western blot analysis of tumor lysates revealed a significant decrease in the level of heat-shock protein 70 in animals treated with C60 + Dox complex. Moreover, the treatment of tumor-bearing mice was accompanied by the increase of cytotoxic activity of immune cells. Thus, the potential mechanisms of antitumor effect of C60 + Dox complex include both its direct action on tumor cells by inducing cell death and increasing of stress sensitivity and an immunomodulating effect. The obtained results provide a scientific basis for further application of C60 + Dox nanocomplexes as treatment agents in cancer chemotherapy.

  7. Draft Genome Sequence of Bacillus selenatarsenatis SF-1T, a Promising Agent for Bioremediation of Environments Contaminated with Selenium and Arsenic.

    PubMed

    Kuroda, Masashi; Ayano, Hiroyuki; Sei, Kazunari; Yamashita, Mitsuo; Ike, Michihiko

    2015-01-01

    Bacillus selenatarsenatis sp. nov. strain SF-1(T) is a promising agent for bioremediation of environments contaminated with selenium and arsenic. Here, we report the draft genome sequence of this strain.

  8. Plant latex: a promising antifungal agent for post harvest disease control.

    PubMed

    Sibi, G; Wadhavan, Rashmi; Singh, Sneha; Shukla, Abhilasha; Dhananjaya, K; Ravikumar, K R; Mallesha, H

    2013-12-01

    Bioactive compounds from plant latex are potential source of antifungic against post harvest pathogens. Latex from a total of seven plant species was investigated for its phytochemical and antifungal properties. Six fungi namely Aspergillus fumigatus, A. niger, A. terreus, F. solani, P. digitatum and R. arrhizus were isolated from infected fruits and vegetables and tested against various solvent extracts of latex. Analysis of latex extracts with phytochemical tests showed the presence of alkaloids, flavonoids, glycosides, phenols, saponins, steroids, tannins and terpenoids. Antifungal assay revealed the potential inhibitory activity of petroleum ether extracts against the postharvest fungal isolates. Various degree of sensitivity was observed irrespective of plant species studied with A. terreus and P. digitatum as the most susceptible ones. F. solani and A. fumigatus were moderately sensitive to the latex extracts tested. Among the plants, latex of Thevetia peruviana (75.2%) and Artocarpus heterophyllus (64.8%) were having potential antifungal activity against the isolates followed by Manilkara zapota (51.1%). In conclusion, use of plant latex makes interest to control postharvest fungal diseases and is fitting well with the concept of safety for human health and environment. PMID:24506041

  9. Plant latex: a promising antifungal agent for post harvest disease control.

    PubMed

    Sibi, G; Wadhavan, Rashmi; Singh, Sneha; Shukla, Abhilasha; Dhananjaya, K; Ravikumar, K R; Mallesha, H

    2013-12-01

    Bioactive compounds from plant latex are potential source of antifungic against post harvest pathogens. Latex from a total of seven plant species was investigated for its phytochemical and antifungal properties. Six fungi namely Aspergillus fumigatus, A. niger, A. terreus, F. solani, P. digitatum and R. arrhizus were isolated from infected fruits and vegetables and tested against various solvent extracts of latex. Analysis of latex extracts with phytochemical tests showed the presence of alkaloids, flavonoids, glycosides, phenols, saponins, steroids, tannins and terpenoids. Antifungal assay revealed the potential inhibitory activity of petroleum ether extracts against the postharvest fungal isolates. Various degree of sensitivity was observed irrespective of plant species studied with A. terreus and P. digitatum as the most susceptible ones. F. solani and A. fumigatus were moderately sensitive to the latex extracts tested. Among the plants, latex of Thevetia peruviana (75.2%) and Artocarpus heterophyllus (64.8%) were having potential antifungal activity against the isolates followed by Manilkara zapota (51.1%). In conclusion, use of plant latex makes interest to control postharvest fungal diseases and is fitting well with the concept of safety for human health and environment.

  10. Copper-64 Labeled Macrobicyclic Sarcophagine Coupled to a GRP Receptor Antagonist Shows Great Promise for PET Imaging of Prostate Cancer.

    PubMed

    Gourni, Eleni; Del Pozzo, Luigi; Kheirallah, Emilie; Smerling, Christiane; Waser, Beatrice; Reubi, Jean-Claude; Paterson, Brett M; Donnelly, Paul S; Meyer, Philipp T; Maecke, Helmut R

    2015-08-01

    The gastrin-releasing peptide receptor (GRPr) is an important molecular target for the visualization and therapy of tumors and can be targeted with radiolabeled bombesin derivatives. The present study aims to develop statine-based bombesin receptor antagonists suitable for labeling with 64Cu for imaging by positron emission tomography (PET). The potent GRPr antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 was conjugated to the sarcophagine (3,6,10,13,16,19-hexaazabicyclo[6.6.6] icosane=Sar) derivative 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar) via PEG4 (LE1) and PEG2 (LE2) spacers and radiolabeled with 64Cu2+ with >95% yield and specific activities of about 100 MBq/nmol. Both Cu(II) conjugates have high affinity for GRPr (IC50: natCu-LE1, 1.4±0.1 nM; natCu-LE2, 3.8±0.6 nM). The antagonistic properties of both conjugates were confirmed by Ca2+-flux measurements. Biodistribution studies of Cu-64-LE1 exhibited specific targeting of the tumor (19.6±4.7% IA/g at 1 h p.i.) and GRPr-positive organs. Biodistribution and PET images at 4 and 24 h postinjection showed increasing tumor-to-background ratios with time. This was illustrated by the acquisition of PET images showing high tumor-to-normal tissue contrast. This study demonstrates the high affinity of the MeCOSar-PEGx-bombesin conjugates to GRPr. The stability of 64Cu complexes of MeCOSar, the long half-life of 64Cu, and the suitable biodistribution profile of the 64Cu-labeled peptides lead to PET images of high contrast suitable for potential translation into the clinic.

  11. DRDE-07 and its analogues as promising cytoprotectants to nitrogen mustard (HN-2)--an alkylating anticancer and chemical warfare agent.

    PubMed

    Sharma, Manoj; Vijayaraghavan, R; Gautam, Anshoo

    2009-08-10

    Nitrogen mustard (HN-2), also known as mechlorethamine, is an alkylating anticancer agent as well as blister inducing chemical warfare agent. We evaluated the cytoprotective efficacy of amifostine, DRDE-07 and their analogues, and other antidotes of mustard agents against HN-2. Administration of 1 LD(50) of HN-2 (20mg/kg) percutaneously, decreased WBC count from 24h onwards. Liver glutathione (GSH) level decreased prominently and the maximum depletion was observed on 7th day post-HN-2 administration. Oxidised glutathione (GSSG) level increased significantly at 24h post-administration and subsequently showed a progressive decrease. Hepatic malondialdehyde (MDA) level and percent DNA damage increased progressively following HN-2 administration. The spleen weight decreased progressively and reached a minimum on 3-4 days with subsequent increase. The antidotes were administered repeatedly for 4 and 8 days after percutaneous administration of single sublethal dose (0.5 and 0.25 LD(50)) of HN-2. Treatment with DRDE-07, DRDE-30 and DRDE-35 significantly protected the changes in spleen weight, WBC count, GSH, GSSG, MDA and DNA damage following HN-2 administration (0.5 and 0.25 LD(50)). There was no alteration in the transaminases (AST and ALT), and alkaline phosphatase (ALP) activities, neither with HN-2 nor with antidotes. The present study shows that HN-2 is highly toxic by percutaneous route and DRDE-07, DRDE-30 and DRDE-35 can partially protect it.

  12. Coral-Associated Bacteria as a Promising Antibiofilm Agent against Methicillin-Resistant and -Susceptible Staphylococcus aureus Biofilms

    PubMed Central

    Gowrishankar, Shanmugaraj; Duncun Mosioma, Nyagwencha; Karutha Pandian, Shunmugiah

    2012-01-01

    The current study deals with the evaluation of two coral-associated bacterial (CAB) extracts to inhibit the biofilm synthesis in vitro as well as the virulence production like hemolysin and exopolysaccharide (EPS), and also to assess their ability to modify the adhesion properties, that is cell surface hydrophobicity (CSH) of methicillin-resistant (MRSA) and -susceptible Staphylococcus aureus (MSSA). Out of nine CAB screened, the ethyl acetate extract of CAB-E2 (Bacillus firmus) and CAB-E4 (Vibrio parahemolyticus) have shown excellent antibiofilm activity against S. aureus. CAB-E2 reduced the production of EPS (57–79%) and hemolysin (43–70%), which ultimately resulted in the significant inhibition of biofilms (80–87%) formed by both MRSA and MSSA. Similarly, CAB-E4 was also found to decrease the production of EPS (43–57%), hemolysin (43–57%) and biofilms (80–85%) of test pathogens. CLSM analysis also proved the antibiofilm efficacy of CAB extracts. Furthermore, the CAB extracts strongly decreased the CSH of S. aureus. Additionally, FT-IR analysis of S. aureus treated with CAB extracts evidenced the reduction in cellular components compared to their respective controls. Thus, the present study reports for the first time, B. firmus—a coral-associated bacterium, as a promising source of antibiofilm agent against the recalcitrant biofilms formed by multidrug resistant S. aureus. PMID:22988476

  13. Narciclasine as well as other Amaryllidaceae isocarbostyrils are promising GTP-ase targeting agents against brain cancers.

    PubMed

    Van Goietsenoven, Gwendoline; Mathieu, Véronique; Lefranc, Florence; Kornienko, Alexander; Evidente, Antonio; Kiss, Robert

    2013-03-01

    The anticancer activity of Amaryllidaceae isocarbostyrils is well documented. At pharmacological concentrations, that is, approximately 1 μM in vitro and approximately 10 mg/kg in vivo, narciclasine displays marked proapoptotic and cytotoxic activity, as does pancratistatin, and significant in vivo anticancer effects in various experimental models, but it is also associated with severe toxic side effects. At physiological doses, that is, approximately 50 nM in vitro and approximately 1 mg/kg in vivo, narciclasine is not cytotoxic but cytostatic and displays marked anticancer activity in vivo in experimental models of brain cancer (including gliomas and brain metastases), but it is not associated with toxic side effects. The cytostatic activity of narciclasine involves the impairment of actin cytoskeleton organization by targeting GTPases, including RhoA and the elongation factor eEF1A. We have demonstrated that chronic treatments of narciclasine (1 mg/kg) significantly increased the survival of immunodeficient mice orthotopically xenografted with highly invasive human glioblastomas and apoptosis-resistant brain metastases, including melanoma- and non-small-cell-lung cancer- (NSCLC) related brain metastases. Thus, narciclasine is a potentially promising agent for the treatment of primary brain cancers and various brain metastases. To date, efforts to develop synthetic analogs with anticancer properties superior to those of narciclasine have failed; thus, research efforts are now focused on narciclasine prodrugs.

  14. 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.

  15. Synthesis of novel hydrazone and azole functionalized pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents.

    PubMed

    Nagender, P; Naresh Kumar, R; Malla Reddy, G; Krishna Swaroop, D; Poornachandra, Y; Ganesh Kumar, C; Narsaiah, B

    2016-09-15

    A series of novel pyrazolo[3,4-b]pyridine based target compounds were synthesized starting from the key intermediate ethyl 2-(3-amino-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetate 5 on reaction with hydrazine hydrate followed by reaction with different aldehydes, acid chlorides and isothiocyanates to form hydrazones 7, oxadiazoles 8, 1,2,4 triazoles 10 and thiadiazoles 11 respectively in high yield. All the final compounds were screened for anticancer activity against four human cancer cell lines. Among them, 1,2,4 triazole derivatives showed promising activity and compound 10d is identified as a lead molecule. PMID:27528432

  16. Synthesis, pharmacological screening and in silico studies of new class of Diclofenac analogues as a promising anti-inflammatory agents.

    PubMed

    Palkar, Mahesh B; Singhai, Anuj S; Ronad, Pradeepkumar M; Vishwanathswamy, A H M; Boreddy, Thippeswamy S; Veerapur, Veeresh P; Shaikh, Mahamadhanif S; Rane, Rajesh A; Karpoormath, Rajshekhar

    2014-05-15

    A novel series of 5-[2-(2,6-dichlorophenylamino)benzyl]-3-(substituted)-1,3,4-oxadiazol-2(3H)-thione (4a-k) derivatives have been synthesized by the Mannich reaction of 5-[2-(2,6-dichlorophenylamino)benzyl]-1,3,4-oxadiazol-2(3H)-thione (3) with an appropriately substituted primary/secondary amines, in the presence of formaldehyde and absolute ethanol. Structures of these novel compounds were characterized on the basis of physicochemical, spectral and elemental analysis. The title compounds (4a-k) were screened for in vivo acute anti-inflammatory and analgesic activities at a dose of 10mg/kg b.w. Compound 4k exhibited the most promising and significant anti-inflammatory profile while compounds 4a, 4d, 4e, 4i, and 4j showed moderate to good inhibitory activity at 2nd and 4thh, respectively. These compounds were also found to have considerable analgesic activity (acetic acid induced writhing model) and antipyretic activity (yeast induced pyrexia model). In addition, the tested compounds were also found to possess less degree of ulcerogenic potential as compared to the standard NSAIDs. Compounds that displayed promising anti-inflammatory profile were further evaluated for their inhibitory activity against cyclooxygenase enzyme (COX-1/COX-2), by colorimetric COX (ovine) inhibitor screening assay method. The results revealed that the compounds 4a, 4e, 4g and 4k exhibited effective inhibition against COX-2. In an attempt to understand the ligand-protein interactions in terms of the binding affinity, docking studies were performed using Molegro Virtual Docker (MVD-2013, 6.0) for those compounds, which showed good anti-inflammatory activity. It was observed that the binding affinities calculated were in agreement with the IC50 values. PMID:24751552

  17. Bacteriophage: Time to Re-Evaluate the Potential of Phage Therapy as a Promising Agent to Control Multidrug-Resistant Bacteria

    PubMed Central

    Sabouri Ghannad, Masoud; Mohammadi, Avid

    2012-01-01

    Nowadays the most difficult problem in treatment of bacterial infections is the appearance of resistant bacteria to the antimicrobial agents so that the attention is being drawn to other potential targets. In view of the positive findings of phage therapy, many advantages have been mentioned which utilizes phage therapy over chemotherapy and it seems to be a promising agent to replace the antibiotics. This review focuses on an understanding of phages for the treatment of bacterial infectious diseases as a new alternative treatment of infections caused by multiple antibiotic resistant bacteria. Therefore, utilizing bacteriophage may be accounted as an alternative therapy. It is appropriate time to re-evaluate the potential of phage therapy as an effective bactericidal and a promising agent to control multidrug-resistant bacteria. PMID:23494063

  18. Phosphorodiamidates as a promising new phosphate prodrug motif for antiviral drug discovery: application to anti-HCV agents.

    PubMed

    McGuigan, Christopher; Madela, Karolina; Aljarah, Mohamed; Bourdin, Claire; Arrica, Maria; Barrett, Emma; Jones, Sarah; Kolykhalov, Alexander; Bleiman, Blair; Bryant, K Dawn; Ganguly, Babita; Gorovits, Elena; Henson, Geoffrey; Hunley, Damound; Hutchins, Jeff; Muhammad, Jerry; Obikhod, Aleksandr; Patti, Joseph; Walters, C Robin; Wang, Jin; Vernachio, John; Ramamurty, Changalvala V S; Battina, Srinivas K; Chamberlain, Stanley

    2011-12-22

    We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterified amino acids, both d and l, and also from various simple amines. All of the compounds were evaluated versus hepatitis C virus in replicon assay, and nanomolar activity levels were observed. Many compounds were noncytotoxic at 100 μM, leading to high antiviral selectivities. The agents are stable in acidic, neutral, and moderately basic media and in selected biological media but show efficient processing by carboxypeptidases and efficiently yield the free nucleoside monophosphate in cells. On the basis of in vitro data, eight leads were selected for additional in vivo evaluation, with the intent of selecting one candidate for progression toward clinical studies. This phosphorodiamidate prodrug method may have broad application outside of HCV and antivirals as it offers many of the advantages of phosphoramidate ProTides but without the chirality issues present in most cases.

  19. Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents.

    PubMed

    Zhu, Jianyong; Wang, Ruimin; Lou, Lanlan; Li, Wei; Tang, Guihua; Bu, Xianzhang; Yin, Sheng

    2016-07-14

    The phytochemical study of Pedilanthus tithymaloides led to the isolation of 13 jatrophane diterpenoids (1-13), of which eight (1-8) are new. Subsequent structural modification of the major components by esterification, hydrolysis, hydrogenation, or epoxidation yielded 22 new derivatives (14-35). Thus, a jatrophane library containing two series of compounds was established to screen for P-glycoprotein (Pgp)-dependent MDR modulators. The activity was evaluated through a combination of Rho123 efflux and chemoreversal assays on adriamycin resistant human hepatocellular carcinoma cell line HepG2 (HepG2/ADR) and adriamycin resistant human breast adenocarcinoma cell line MCF-7 (MCF-7/ADR). Compounds 19, 25, and 26 were identified as potent MDR modulators with greater chemoreversal ability and less cytotoxicity than the third-generation drug tariquidar. The structure-activity relationship (SAR) was discussed, which showed that modifications beyond just increasing the lipophilicity of this class of Pgp inhibitors are beneficial to the activity. Compound 26, which exhibited a remarkable metabolic stability in vitro and a favorable antitumor effect in vivo, would serve as a promising lead for the development of new MDR reversal agents. PMID:27328029

  20. Single agent carboplatin for pediatric low-grade glioma: A retrospective analysis shows equivalent efficacy to multiagent chemotherapy.

    PubMed

    Dodgshun, Andrew J; Maixner, Wirginia J; Heath, John A; Sullivan, Michael J; Hansford, Jordan R

    2016-01-15

    Pediatric low-grade gliomas (LGG) that are unresectable often require adjuvant chemotherapy such as carboplatin/vincristine. Small Phase II studies have suggested equivalent efficacy of single agent 4-weekly carboplatin. A single-institution retrospective review captured all patients aged 0 to 18 years diagnosed with LGG between 1996 and 2013 and treated with carboplatin monotherapy. The response and survival according to tumor site was compared to published results for multiagent chemotherapy. Of 268 children diagnosed with LGG diagnosed in this period, 117 received chemotherapy and 104 children received single agent carboplatin as first line chemotherapy. All patients received carboplatin at 560 mg/m(2), four-weekly for a median of 12 courses. The mean age at diagnosis was 5.8 years (range 3m-16y) and 32% had neurofibromatosis type 1. With a mean followup of 54 months, 86% of patients achieved stabilisation or better (SD/PR/CR). 3-year progression free survival (PFS) 66% (95% CI 57-76%), and 5-year PFS was 51% (95% CI 41-63%). 5-year overall survival was 97%. Multivariate analysis showed poorer PFS for those with chiasmatic/hypothalamic tumors. In this retrospective analysis single agent carboplatin shows comparable efficacy to historical multiagent chemotherapy for the treatment of patients with unresectable LGG. Equivalent outcomes are achieved with less chemotherapy, reduced side effects and fewer hospital visits. Further research is required to establish the place of this simplified regimen in the up-front treatment of unresectable LGG.

  1. Towards Personalized Treatment of Prostate Cancer: PSMA I&T, a Promising Prostate-Specific Membrane Antigen-Targeted Theranostic Agent

    PubMed Central

    Chatalic, Kristell L.S.; Heskamp, Sandra; Konijnenberg, Mark; Molkenboer-Kuenen, Janneke D.M.; Franssen, Gerben M.; Clahsen-van Groningen, Marian C.; Schottelius, Margret; Wester, Hans-Jürgen; van Weerden, Wytske M.; Boerman, Otto C.; de Jong, Marion

    2016-01-01

    Prostate-specific membrane antigen (PSMA) is a well-established target for nuclear imaging and therapy of prostate cancer (PCa). Radiolabeled small-molecule PSMA inhibitors are excellent candidates for PCa theranostics—they rapidly and efficiently localize in tumor lesions. However, high tracer uptake in kidneys and salivary glands are major concerns for therapeutic applications. Here, we present the preclinical application of PSMA I&T, a DOTAGA-chelated urea-based PSMA inhibitor, for SPECT/CT imaging and radionuclide therapy of PCa. 111In-PSMA I&T showed dose-dependent uptake in PSMA-expressing tumors, kidneys, spleen, adrenals, lungs and salivary glands. Coadministration of 2-(phosphonomethyl)pentane-1,5-dioic acid (2-PMPA) efficiently reduced PSMA-mediated renal uptake of 111In-PSMA I&T, with the highest tumor/kidney radioactivity ratios being obtained using a dose of 50 nmol 2-PMPA. SPECT/CT clearly visualized subcutaneous tumors and sub-millimeter intraperitoneal metastases; however, high renal and spleen uptake in control mice (no 2-PMPA) interfered with visualization of metastases in the vicinity of those organs. Coadministration of 2-PMPA increased the tumor-to-kidney absorbed dose ratio during 177Lu-PSMA I&T radionuclide therapy. Hence, at equivalent absorbed dose to the tumor (36 Gy), coinjection of 2-PMPA decreased absorbed dose to the kidneys from 30 Gy to 12 Gy. Mice injected with 177Lu-PSMA I&T only, showed signs of nephrotoxicity at 3 months after therapy, whereas mice injected with 177Lu-PSMA I&T + 2-PMPA did not. These data indicate that PSMA I&T is a promising theranostic tool for PCa. PSMA-specific uptake in kidneys can be successfully tackled using blocking agents such as 2-PMPA. PMID:27162555

  2. Combination therapy of RY10-4 with the γ-secretase inhibitor DAPT shows promise in treating HER2-amplified breast cancer

    PubMed Central

    Su, Feng; Zhu, Shilin; Ruan, Jinlan; Muftuoglu, Yagmur; Zhang, Longbo; Yuan, Qianying

    2016-01-01

    RY10-4, a novel protoapigenone analog, shows potent cytotoxicity against human breast cancer cells. However, breast cancer cell lines overexpressing human epidermal growth factor receptor 2 (HER2), SKBR3 and BT474, showed less sensitivity to RY10-4 when compared to breast cancer cells lines expressing lower levels of HER2, such as MDA-MB-231 and MCF-7 cells. This was associated with aberrant hyperactivity in Notch signaling in cells treated with RY10-4, since treatment with RY10-4 causes an increase in Notch activity by 2-to3.5-fold in SKBR3 and BT474 cell lines. The increase in activity was abrogated with a γ-secretase inhibitor, DAPT, or with Notch1 small-interfering RNA (si-Notch1). Cell proliferation was inhibited more effectively by RY10-4 plus DAPT or si-Notch1 than either agent alone. RY10-4 plus DAPT increases apoptosis in both HER2-overexpressing cell lines by two-fold compared to RY10-4 alone, while DAPT alone has no significant effects on apoptosis. In addition, we previously found RY10-4 could inhibit tumor growth through the PI3K/AKT pathway. Here we report that the combination of RY10-4 and DAPT exhibit additive suppression on AKT phosphorylation, contributing to the anti-cancer effects. In an animal model, this combination therapy inhibits the growth of SKBR3 tumor xenografts in nude mice to a greater extent than treatment with either reagent alone. These results indicate that the aberrant activation of Notch signaling impedes the inhibitory effect of RY10-4 on HER2-amplified cell proliferation. Furthermore, these adverse effects can be prevented by treatment combining RY10-4 with a Notch pathway inhibitor. PMID:26716652

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

    PubMed

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

    2016-03-01

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

  4. Description of a new species of Anagyrus Howard (Hymenoptera: Chalcidoidea: Encyrtidae), a promising biological control agent of the invasive Madeira mealybug, Phenacoccus madeirensis Green (Hemiptera: Sternorrhyncha: Pseudococcidae).

    PubMed

    Rameshkumar, A; Noyes, J S; Poorani, J; Chong, J H

    2013-01-01

    Anagyrus amnestos sp. n. (Hymenoptera: Encyrtidae), a promising parasitoid of the invasive Madeira mealybug, Phenacoccus madeirensis Green (Hemiptera: Pseudococcidae), is described based on material collected from India. This parasitoid was identified as Anagyrus sp. nov. nr. sinope Noyes & Menezes in recent literature, and was initially collected in Georgia, USA. It was found to be a specific parasitoid of the Madeira mealybug and its biological attributes and potential as a biological control agent of this pest were studied. In what appears to be a case of fortuitous introduction, we detected this parasitoid in large numbers on Madeira mealybugs from the southern Indian state of Karnataka, where the mealybug is a recently introduced invasive pest. In view of its economic importance as a potential biological control agent of the Madeira mealybug, it is formally described and illustrated here. Comparative accounts of the new species vis-a-vis its close relatives in India and the Americas are provided.

  5. Description of a new species of Anagyrus Howard (Hymenoptera: Chalcidoidea: Encyrtidae), a promising biological control agent of the invasive Madeira mealybug, Phenacoccus madeirensis Green (Hemiptera: Sternorrhyncha: Pseudococcidae).

    PubMed

    Rameshkumar, A; Noyes, J S; Poorani, J; Chong, J H

    2013-01-01

    Anagyrus amnestos sp. n. (Hymenoptera: Encyrtidae), a promising parasitoid of the invasive Madeira mealybug, Phenacoccus madeirensis Green (Hemiptera: Pseudococcidae), is described based on material collected from India. This parasitoid was identified as Anagyrus sp. nov. nr. sinope Noyes & Menezes in recent literature, and was initially collected in Georgia, USA. It was found to be a specific parasitoid of the Madeira mealybug and its biological attributes and potential as a biological control agent of this pest were studied. In what appears to be a case of fortuitous introduction, we detected this parasitoid in large numbers on Madeira mealybugs from the southern Indian state of Karnataka, where the mealybug is a recently introduced invasive pest. In view of its economic importance as a potential biological control agent of the Madeira mealybug, it is formally described and illustrated here. Comparative accounts of the new species vis-a-vis its close relatives in India and the Americas are provided. PMID:26176096

  6. Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells.

    PubMed

    Sharma, Monika; Tuaine, Jo; McLaren, Blair; Waters, Debra L; Black, Katherine; Jones, Lynnette M; McCormick, Sally P A

    2016-01-01

    Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

  7. Rapamycin and Chloroquine: The In Vitro and In Vivo Effects of Autophagy-Modifying Drugs Show Promising Results in Valosin Containing Protein Multisystem Proteinopathy

    PubMed Central

    Nalbandian, Angèle; Llewellyn, Katrina J.; Nguyen, Christopher; Yazdi, Puya G.; Kimonis, Virginia E.

    2015-01-01

    Mutations in the valosin containing protein (VCP) gene cause hereditary Inclusion body myopathy (hIBM) associated with Paget disease of bone (PDB), frontotemporal dementia (FTD), more recently termed multisystem proteinopathy (MSP). Affected individuals exhibit scapular winging and die from progressive muscle weakness, and cardiac and respiratory failure, typically in their 40s to 50s. Histologically, patients show the presence of rimmed vacuoles and TAR DNA-binding protein 43 (TDP-43)-positive large ubiquitinated inclusion bodies in the muscles. We have generated a VCPR155H/+ mouse model which recapitulates the disease phenotype and impaired autophagy typically observed in patients with VCP disease. Autophagy-modifying agents, such as rapamycin and chloroquine, at pharmacological doses have previously shown to alter the autophagic flux. Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCPR155H/+ mice. Rapamycin-treated mice demonstrated significant improvement in muscle performance, quadriceps histological analysis, and rescue of ubiquitin, and TDP-43 pathology and defective autophagy as indicated by decreased protein expression levels of LC3-I/II, p62/SQSTM1, optineurin and inhibiting the mTORC1 substrates. Conversely, chloroquine-treated VCPR155H/+ mice revealed progressive muscle weakness, cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-I/II, p62/SQSTM1, and optineurin expression levels. Our in vitro patient myoblasts studies treated with rapamycin demonstrated an overall improvement in the autophagy markers. Targeting the mTOR pathway ameliorates an increasing list of disorders, and these findings suggest that VCP disease and related neurodegenerative multisystem proteinopathies can

  8. Novel alkylphospholipid-DTC hybrids as promising agents against endocrine related cancers acting via modulation of Akt-pathway.

    PubMed

    Jangir, Santosh; Bala, Veenu; Lal, Nand; Kumar, Lalit; Sarswat, Amit; Kumar, Amit; Hamidullah; Saini, Karan S; Sharma, Vikas; Verma, Vikas; Maikhuri, Jagdamba P; Konwar, Rituraj; Gupta, Gopal; Sharma, Vishnu L

    2014-10-01

    A new series of 2-(alkoxy(hydroxy)phosphoryloxy)ethyl dialkylcarbodithioate derivatives was synthesized and evaluated against endocrine related cancers, acting via modulation of Akt-pathway. Eighteen compounds were active at 7.24-100 μM against MDA-MB-231 or MCF-7 cell lines of breast cancer. Three compounds (14, 18 and 22) were active against MCF-7 cells at IC50 significantly better than miltefosine and most of the compounds were less toxic towards non-cancer cell lines, HEK-293. On the other hand, twelve compounds exhibited cell growth inhibiting activity against prostate cancer cell lines, either PC-3 or DU-145 at 14.69-95.20 μM. While nine of these were active against both cell lines. The most promising compounds 14 and 18 were about two and five fold more active than miltefosine against DU-145 and MCF-7 cell lines respectively and significantly down regulated phospho-Akt. Possibly anti-cancer and pro-apoptotic activity was mostly due to blockade of Akt-pathway.

  9. The vascular disrupting agent ZD6126 shows increased antitumor efficacy and enhanced radiation response in large, advanced tumors

    SciTech Connect

    Siemann, Dietmar W. . E-mail: siemadw@ufl.edu; Rojiani, Amyn M.

    2005-07-01

    Purpose: ZD6126 is a vascular-targeting agent that induces selective effects on the morphology of proliferating and immature endothelial cells by disrupting the tubulin cytoskeleton. The efficacy of ZD6126 was investigated in large vs. small tumors in a variety of animal models. Methods and Materials: Three rodent tumor models (KHT, SCCVII, RIF-1) and three human tumor xenografts (Caki-1, KSY-1, SKBR3) were used. Mice bearing leg tumors ranging in size from 0.1-2.0 g were injected intraperitoneally with a single 150 mg/kg dose of ZD6126. The response was assessed by morphologic and morphometric means as well as an in vivo to in vitro clonogenic cell survival assay. To examine the impact of tumor size on the extent of enhancement of radiation efficacy by ZD6126, KHT sarcomas of three different sizes were irradiated locally with a range of radiation doses, and cell survival was determined. Results: All rodent tumors and human tumor xenografts evaluated showed a strong correlation between increasing tumor size and treatment effect as determined by clonogenic cell survival. Detailed evaluation of KHT sarcomas treated with ZD6126 showed a reduction in patent tumor blood vessels that was {approx}20% in small (<0.3 g) vs. >90% in large (>1.0 g) tumors. Histologic assessment revealed that the extent of tumor necrosis after ZD6126 treatment, although minimal in small KHT sarcomas, became more extensive with increasing tumor size. Clonogenic cell survival after ZD6126 exposure showed a decrease in tumor surviving fraction from approximately 3 x 10{sup -1} to 1 x 10{sup -4} with increasing tumor size. When combined with radiotherapy, ZD6126 treatment resulted in little enhancement of the antitumor effect of radiation in small (<0.3 g) tumors but marked increases in cell kill in tumors larger than 1.0 g. Conclusions: Because bulky neoplastic disease is typically the most difficult to manage, the present findings provide further support for the continued development of vascular

  10. High affinity and covalent-binding microtubule stabilizing agents show activity in chemotherapy-resistant acute myeloid leukemia cells

    PubMed Central

    Pera, Benet; Calvo-Vidal, M. Nieves; Ambati, Srikanth; Jordi, Michel; Kahn, Alissa; Díaz, J. Fernando; Fang, Weishuo; Altmann, Karl-Heinz; Cerchietti, Leandro; Moore, Malcolm A.S.

    2016-01-01

    Treatment failure in acute myeloid leukemia (AML) is frequently due to the persistence of a cell population resistant to chemotherapy through different mechanisms, in which drug efflux via ATP-binding cassette (ABC) proteins, specifically P-glycoprotein, is one of the most recognized. However, disappointing results from clinical trials employing inhibitors for these transporters have demonstrated the need to adopt different strategies. We hypothesized that microtubule targeting compounds presenting high affinity or covalent binding could overcome the effect of ABC transporters. We therefore evaluated the activity of the high-affinity paclitaxel analog CTX-40 as well as the covalent binder zampanolide (ZMP) in AML cells. Both molecules were active in chemosensitive as well as in chemoresistant cell lines overexpressing P-glycoprotein. Moreover, ZMP or CTX-40 in combination with daunorubicin showed synergistic killing without increased in vitro hematopoietic toxicity. In a primary AML sample, we further demonstrated that ZMP and CTX-40 are active in progenitor and differentiated leukemia cell populations. In sum, our data indicate that high affinity and covalent-binding anti-microtubule agents are active in AML cells otherwise chemotherapy resistant. PMID:26277539

  11. New TiAg composite coating for bone prosthesis engineering shows promising microvascular compatibility in the murine dorsal skinfold chamber model.

    PubMed

    Behrendt, Ann-Kathrin; Beythien, Maximilian; Huber, Jakob; Zufraß, Thorsten; Butschkau, Antje; Mittlmeier, Thomas; Vollmar, Brigitte

    2015-01-01

    The incorporation of antimicrobial substances like silver into implant surface coatings is one promising concept against primary infections of endoprosthesis, especially for immunocompromised patients as well as against reinfection after revision operations. However, besides good antimicrobial and mechanical properties it is equally important that the implant material does not disturb the local microvascular perfusion of muscle tissue to enable microbial host defense and tissue repair processes. In this study the biocompatibility of a newly developed TiAg-composite coating applied on conventional titanium via physical vapor deposition was analysed. To evaluate the local microvascular and inflammatory response of striated muscle tissue upon implantation of TiAg-coated plates the murine dorsal skinfold chamber model was used. We repetitively examined local capillary and venular perfusion, endothelial integrity as well as leucocyte activation by intravital fluorescence microscopy at 1 h, 24 h as well as 3 and 7 days after implantation. TiAg-implants were well tolerated by the vascular system as indicated by intact functional capillary density and endothelial integrity compared to pure titanium plates and controls without a metal implant. Furthermore, quantification of rolling and adherent leucocytes did not reveal signs of inflammation upon TiAg-implantation.

  12. The 60th ASCD Annual Conference and Exhibit Show 2005, 2-4 April 2005: "Voices of Education--Unleashing the Power, Passion and Promise"

    ERIC Educational Resources Information Center

    Roberts, Brian

    2005-01-01

    Purpose: Aims to report on the 60th ASCD Annual Conference and Exhibit Show 2005, held in Orlando Florida, 2-4 April 2005 by the Association for Supervision and Curriculum Development. Design/methodology/approach: Discusses the presentations such as the obesity epidemic in children, educational progress in schools, creating capacity for learning,…

  13. PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects

    PubMed Central

    Zazo, Sandra; Arpí, Oriol; Menéndez, Silvia; Manso, Rebeca; Lluch, Ana; Eroles, Pilar; Rovira, Ana; Albanell, Joan; García-Foncillas, Jesús; Madoz-Gúrpide, Juan; Rojo, Federico

    2015-01-01

    The protein phosphatase 2A (PP2A) is a key tumor suppressor which has emerged as a novel molecular target in some human cancers. Here, we show that PP2A inhibition is a common event in breast cancer and identified PP2A phosphorylation and deregulation SET and CIP2A as molecular contributing mechanisms to inactivate PP2A. Interestingly, restoration of PP2A activity after FTY720 treatment reduced cell growth, induced apoptosis and decreased AKT and ERK activation. Moreover, FTY720 led to PP2A activation then enhancing doxorubicin-induced antitumor effects both in vitro and in vivo. PP2A inhibition (CPscore: PP2A phosphorylation and/or CIP2A overexpression) was detected in 27% of cases (62/230), and associated with grade (p = 0.017), relapse (p < 0.001), negative estrogen (p < 0.001) and progesterone receptor expression (p < 0.001), HER2-positive tumors (p = 0.049), Ki-67 expression (p < 0.001), and higher AKT (p < 0.001) and ERK (p < 0.001) phosphorylation. Moreover, PP2A inhibition determined shorter overall (p = 0.006) and event-free survival (p = 0.003), and multivariate analysis confirmed its independent prognostic impact. Altogether, our results indicate that PP2A is frequently inactivated in breast cancer and determines worse outcome, and its restoration using PP2A activators represents an alternative therapeutic strategy in this disease. PMID:25726524

  14. Iron oxide nanoparticles show no toxicity in the comet assay in lymphocytes: A promising vehicle as a nitric oxide releasing nanocarrier in biomedical applications

    NASA Astrophysics Data System (ADS)

    de Lima, R.; Oliveira, J. L.; Murakami, P. S. K.; Molina, M. A. M.; Itri, R.; Haddad, P.; Seabra, A. B.

    2013-04-01

    This work reports the synthesis and toxicological evaluation of surface modified magnetic iron oxide nanoparticles as vehicles to carry and deliver nitric oxide (NO). The surface of the magnetic nanoparticles (MNPs) was coated with two thiol-containing hydrophilic ligands: mercaptosuccinic acid (MSA) or dimercaptosuccinic acid (DMSA), leading to thiolated MNPs. Free thiols groups on the surface of MSA- or DMSA-MNPs were nitrosated leading to NO-releasing MNPs. The genotoxicity of thiolated-coated MNPs was evaluated towards human lymphocyte cells by the comet assay. No genotoxicity was observed due to exposure of human lymphocytes to MSA- or DMSA-MNPs, indicating that these nanovectors can be used as inert vehicles in drug delivery, in biomedical applications. On the other hand, NO-releasing MPNs showed genotoxicity and apoptotic activities towards human lymphocyte cell cultures. These results indicate that NO-releasing MNPs may result in important biomedical applications, such as the treatment of tumors, in which MNPs can be guided to the target site through the application of an external magnetic field, and release NO directly to the desired site of action.

  15. EXPERT SYSTEMS SHOW PROMISE FOR CUSTOMER INQUIRIES

    EPA Science Inventory

    This article describes results of an agreement between the North Penn Water Authority in Lansdale, Pa., and the US Environmental Protection Agency, Drinking Water Research Division, Cincinnati, Ohio, to study use of expert systems technology in a water utility. The threeyear stud...

  16. Drug Trio Shows Major Promise Against Myeloma

    MedlinePlus

    ... 19 percent. The drug, which is given by infusion, latches onto a specific protein on myeloma cells ... and Drug Administration, the most common ones include infusion-related reactions, fatigue, nausea, back pain and fever. ...

  17. For Problem Drinkers, Experimental Drug Shows Promise

    MedlinePlus

    ... the U.S. National Institute on Alcohol Abuse and Alcoholism assessed the drug in a 12-week clinical ... Services, or federal policy. More Health News on: Alcoholism and Alcohol Abuse Medicines Recent Health News Related ...

  18. Experimental Genital Herpes Drug Shows Promise

    MedlinePlus

    ... be presented Monday at an American Society for Microbiology meeting in Boston. Research presented at meetings is ... currently achievable," Fife said. SOURCE: American Society for Microbiology, news release, June 20, 2016 HealthDay Copyright (c) ...

  19. Storing CO2 underground shows promising results

    NASA Astrophysics Data System (ADS)

    Zweigel, Peter; Gale, John

    Long-term underground storage of CO2 is an important element in concepts to reduce atmospheric CO2 emissions as the use of fossil fuels continues. The first results of a multinational research project evaluating the injection of CO2 into a saline aquifer in the North Sea are validating this method of CO2 reduction, and are serving to further define the research needed to develop the technology for large-scale applicability. Reducing the emission of substances that have potentially harmful effects on global climate— for example, CO2—has become a central issue of environmental policy at least since the 1997 Kyoto conference on climate change.

  20. Compact gas meter development shows promise

    SciTech Connect

    Norman, R.S.

    1995-07-01

    In the mid-1980s, the Gas Research Institute (GRI) surveyed the needs of the natural gas industry to determine where improved operations technology would assist the industry in the residential gas market. A compact gas meter was identified as an advance in the metering area which would be beneficial for future growth of natural gas usage, especially in the multi-family construction area. GRI currently is pursuing development of a compact diaphragm meter and evaluating several advanced electronic meters for future use in the US. Overall benefits to the natural gas distribution industry will be: greater installation flexibility for a smaller meter; easier integration with automatic meter reading equipment; lower total installation costs including meter, meter supports, and regulator; better appearance in confined, exterior installations. Smaller gas meters will become a viable option for gas companies, builders, and contractors i the near future and will enhance gas energy use for many residential and commercial buildings within the next five years. GRI`s overall goal is to have 50,000 compact gas meters installed in the US by the end of 1997.

  1. IPI-145 shows promise in CLL patients.

    PubMed

    2014-02-01

    Results from a phase I study of Infinity Pharmaceuticals' IPI-145, which inhibits both δ and γ isoforms of phosphoinositide3-kinase, suggest the drug is safe and effective in patients with advanced chronic lymphocytic leukemia. PMID:24501284

  2. Keeping Promises

    NASA Technical Reports Server (NTRS)

    Howell, Gregory A.

    2005-01-01

    Commitments are between people, not schedules. Project management as practiced today creates a "commitment-free zone," because it assumes that people will commit to centrally managed schedules without providing a mechanism to ensure their work can be done. So they give it their best, but something always seems to come up ..."I tried, but you know how it is." This form of project management does not provide a mechanism to ensure that what should be done, can in fact be done at the required moment. Too often, promises reliable promise. made in coordination meetings are conditional and unreliable. It has been my experience that at times trust can be low and hard to build in this environment. The absence of reliable promises explains why on well-run projects, people are often only completing 30-50 percent of the deliverables they d promised for the week. We all know what a promise is; we have plenty of experience making them and receiving them from others. So what s the problem? The sad fact is that the project environment-like many other work environments- is often so filled with systemic dishonesty, that we don t expect promises that are reliable. Project managers excel when they manage their projects as networks of commitments and help their people learn to elicit and make reliable promises.

  3. A High-Throughput In Vitro Drug Screen in a Genetically Engineered Mouse Model of Diffuse Intrinsic Pontine Glioma Identifies BMS-754807 as a Promising Therapeutic Agent

    PubMed Central

    Halvorson, Kyle G.; Barton, Kelly L.; Schroeder, Kristin; Misuraca, Katherine L.; Hoeman, Christine; Chung, Alex; Crabtree, Donna M.; Cordero, Francisco J.; Singh, Raj; Spasojevic, Ivan; Berlow, Noah; Pal, Ranadip; Becher, Oren J.

    2015-01-01

    Diffuse intrinsic pontine gliomas (DIPGs) represent a particularly lethal type of pediatric brain cancer with no effective therapeutic options. Our laboratory has previously reported the development of genetically engineered DIPG mouse models using the RCAS/tv-a system, including a model driven by PDGF-B, H3.3K27M, and p53 loss. These models can serve as a platform in which to test novel therapeutics prior to the initiation of human clinical trials. In this study, an in vitro high-throughput drug screen as part of the DIPG preclinical consortium using cell-lines derived from our DIPG models identified BMS-754807 as a drug of interest in DIPG. BMS-754807 is a potent and reversible small molecule multi-kinase inhibitor with many targets including IGF-1R, IR, MET, TRKA, TRKB, AURKA, AURKB. In vitro evaluation showed significant cytotoxic effects with an IC50 of 0.13 μM, significant inhibition of proliferation at a concentration of 1.5 μM, as well as inhibition of AKT activation. Interestingly, IGF-1R signaling was absent in serum-free cultures from the PDGF-B; H3.3K27M; p53 deficient model suggesting that the antitumor activity of BMS-754807 in this model is independent of IGF-1R. In vivo, systemic administration of BMS-754807 to DIPG-bearing mice did not prolong survival. Pharmacokinetic analysis demonstrated that tumor tissue drug concentrations of BMS-754807 were well below the identified IC50, suggesting that inadequate drug delivery may limit in vivo efficacy. In summary, an unbiased in vitro drug screen identified BMS-754807 as a potential therapeutic agent in DIPG, but BMS-754807 treatment in vivo by systemic delivery did not significantly prolong survival of DIPG-bearing mice. PMID:25748921

  4. Could the FDA-approved anti-HIV PR inhibitors be promising anticancer agents? An answer from enhanced docking approach and molecular dynamics analyses.

    PubMed

    Arodola, Olayide A; Soliman, Mahmoud E S

    2015-01-01

    Based on experimental data, the anticancer activity of nelfinavir (NFV), a US Food and Drug Administration (FDA)-approved HIV-1 protease inhibitor (PI), was reported. Nevertheless, the mechanism of action of NFV is yet to be verified. It was hypothesized that the anticancer activity of NFV is due to its inhibitory effect on heat shock protein 90 (Hsp90), a promising target for anticancer therapy. Such findings prompted us to investigate the potential anticancer activity of all other FDA-approved HIV-1 PIs against human Hsp90. To accomplish this, "loop docking" - an enhanced in-house developed molecular docking approach - followed by molecular dynamic simulations and postdynamic analyses were performed to elaborate on the binding mechanism and relative binding affinities of nine FDA-approved HIV-1 PIs against human Hsp90. Due to the lack of the X-ray crystal structure of human Hsp90, homology modeling was performed to create its 3D structure for subsequent simulations. Results showed that NFV has better binding affinity (ΔG =-9.2 kcal/mol) when compared with other PIs: this is in a reasonable accordance with the experimental data (IC50 3.1 μM). Indinavir, saquinavir, and ritonavir have close binding affinity to NFV (ΔG =-9.0, -8.6, and -8.5 kcal/mol, respectively). Per-residue interaction energy decomposition analysis showed that hydrophobic interaction (most importantly with Val534 and Met602) played the most predominant role in drug binding. To further validate the docking outcome, 5 ns molecular dynamic simulations were performed in order to assess the stability of the docked complexes. To our knowledge, this is the first account of detailed computational investigations aimed to investigate the potential anticancer activity and the binding mechanism of the FDA-approved HIV PIs binding to human Hsp90. Information gained from this study should also provide a route map toward the design, optimization, and further experimental investigation of potential

  5. Could the FDA-approved anti-HIV PR inhibitors be promising anticancer agents? An answer from enhanced docking approach and molecular dynamics analyses

    PubMed Central

    Arodola, Olayide A; Soliman, Mahmoud ES

    2015-01-01

    Based on experimental data, the anticancer activity of nelfinavir (NFV), a US Food and Drug Administration (FDA)-approved HIV-1 protease inhibitor (PI), was reported. Nevertheless, the mechanism of action of NFV is yet to be verified. It was hypothesized that the anticancer activity of NFV is due to its inhibitory effect on heat shock protein 90 (Hsp90), a promising target for anticancer therapy. Such findings prompted us to investigate the potential anticancer activity of all other FDA-approved HIV-1 PIs against human Hsp90. To accomplish this, “loop docking” – an enhanced in-house developed molecular docking approach – followed by molecular dynamic simulations and postdynamic analyses were performed to elaborate on the binding mechanism and relative binding affinities of nine FDA-approved HIV-1 PIs against human Hsp90. Due to the lack of the X-ray crystal structure of human Hsp90, homology modeling was performed to create its 3D structure for subsequent simulations. Results showed that NFV has better binding affinity (ΔG =−9.2 kcal/mol) when compared with other PIs: this is in a reasonable accordance with the experimental data (IC50 3.1 μM). Indinavir, saquinavir, and ritonavir have close binding affinity to NFV (ΔG =−9.0, −8.6, and −8.5 kcal/mol, respectively). Per-residue interaction energy decomposition analysis showed that hydrophobic interaction (most importantly with Val534 and Met602) played the most predominant role in drug binding. To further validate the docking outcome, 5 ns molecular dynamic simulations were performed in order to assess the stability of the docked complexes. To our knowledge, this is the first account of detailed computational investigations aimed to investigate the potential anticancer activity and the binding mechanism of the FDA-approved HIV PIs binding to human Hsp90. Information gained from this study should also provide a route map toward the design, optimization, and further experimental investigation of

  6. Could the FDA-approved anti-HIV PR inhibitors be promising anticancer agents? An answer from enhanced docking approach and molecular dynamics analyses.

    PubMed

    Arodola, Olayide A; Soliman, Mahmoud E S

    2015-01-01

    Based on experimental data, the anticancer activity of nelfinavir (NFV), a US Food and Drug Administration (FDA)-approved HIV-1 protease inhibitor (PI), was reported. Nevertheless, the mechanism of action of NFV is yet to be verified. It was hypothesized that the anticancer activity of NFV is due to its inhibitory effect on heat shock protein 90 (Hsp90), a promising target for anticancer therapy. Such findings prompted us to investigate the potential anticancer activity of all other FDA-approved HIV-1 PIs against human Hsp90. To accomplish this, "loop docking" - an enhanced in-house developed molecular docking approach - followed by molecular dynamic simulations and postdynamic analyses were performed to elaborate on the binding mechanism and relative binding affinities of nine FDA-approved HIV-1 PIs against human Hsp90. Due to the lack of the X-ray crystal structure of human Hsp90, homology modeling was performed to create its 3D structure for subsequent simulations. Results showed that NFV has better binding affinity (ΔG =-9.2 kcal/mol) when compared with other PIs: this is in a reasonable accordance with the experimental data (IC50 3.1 μM). Indinavir, saquinavir, and ritonavir have close binding affinity to NFV (ΔG =-9.0, -8.6, and -8.5 kcal/mol, respectively). Per-residue interaction energy decomposition analysis showed that hydrophobic interaction (most importantly with Val534 and Met602) played the most predominant role in drug binding. To further validate the docking outcome, 5 ns molecular dynamic simulations were performed in order to assess the stability of the docked complexes. To our knowledge, this is the first account of detailed computational investigations aimed to investigate the potential anticancer activity and the binding mechanism of the FDA-approved HIV PIs binding to human Hsp90. Information gained from this study should also provide a route map toward the design, optimization, and further experimental investigation of potential

  7. 4,6-Diphenylpyridines as Promising Novel Anti-Influenza Agents Targeting the PA-PB1 Protein-Protein Interaction: Structure-Activity Relationships Exploration with the Aid of Molecular Modeling.

    PubMed

    Trist, Iuni M L; Nannetti, Giulio; Tintori, Cristina; Fallacara, Anna Lucia; Deodato, Davide; Mercorelli, Beatrice; Palù, Giorgio; Wijtmans, Maikel; Gospodova, Tzveta; Edink, Ewald; Verheij, Mark; de Esch, Iwan; Viteva, Lilia; Loregian, Arianna; Botta, Maurizio

    2016-03-24

    Influenza is an infectious disease that represents an important public health burden, with high impact on the global morbidity, mortality, and economy. The poor protection and the need of annual updating of the anti-influenza vaccine, added to the rapid emergence of viral strains resistant to current therapy make the need for antiviral drugs with novel mechanisms of action compelling. In this regard, the viral RNA polymerase is an attractive target that allows the design of selective compounds with reduced risk of resistance. In previous studies we showed that the inhibition of the polymerase acidic protein-basic protein 1 (PA-PB1) interaction is a promising strategy for the development of anti-influenza agents. Starting from the previously identified 3-cyano-4,6-diphenyl-pyridines, we chemically modified this scaffold and explored its structure-activity relationships. Noncytotoxic compounds with both the ability of disrupting the PA-PB1 interaction and antiviral activity were identified, and their mechanism of target binding was clarified with molecular modeling simulations. PMID:26924568

  8. Facile synthesis of water-dispersible Cu2O nanocrystal-reduced graphene oxide hybrid as a promising cancer therapeutic agent

    NASA Astrophysics Data System (ADS)

    Hou, Chengyi; Quan, Haocheng; Duan, Yourong; Zhang, Qinghong; Wang, Hongzhi; Li, Yaogang

    2013-01-01

    We report a Cu2O nanocrystal-reduced graphene oxide hybrid that is dispersible in water and has anticancer activity under both visible and near-infrared light irradiation. In contrast to the highly efficient killing of both normal and cancer cells initiated by the photothermal effect, the photocatalytic effect of this material results in the selective killing of cancer cells under visible light irradiation. These results have implications for safe and widely applicable cancer therapy agents.We report a Cu2O nanocrystal-reduced graphene oxide hybrid that is dispersible in water and has anticancer activity under both visible and near-infrared light irradiation. In contrast to the highly efficient killing of both normal and cancer cells initiated by the photothermal effect, the photocatalytic effect of this material results in the selective killing of cancer cells under visible light irradiation. These results have implications for safe and widely applicable cancer therapy agents. Electronic supplementary information (ESI) available: Characterization of the over-reduced products and the photocatalytic activity of the CRGO. See DOI: 10.1039/c2nr32938g

  9. Bioactive compounds of Crocus sativus L. and their semi-synthetic derivatives as promising anti-Helicobacter pylori, anti-malarial and anti-leishmanial agents.

    PubMed

    De Monte, Celeste; Bizzarri, Bruna; Gidaro, Maria Concetta; Carradori, Simone; Mollica, Adriano; Luisi, Grazia; Granese, Arianna; Alcaro, Stefano; Costa, Giosuè; Basilico, Nicoletta; Parapini, Silvia; Scaltrito, Maria Maddalena; Masia, Carla; Sisto, Francesca

    2015-12-01

    Crocus sativus L. is known in herbal medicine for the various pharmacological effects of its components, but no data are found in literature about its biological properties toward Helicobacter pylori, Plasmodium spp. and Leishmania spp. In this work, the potential anti-bacterial and anti-parasitic effects of crocin and safranal, two important bioactive components in C. sativus, were explored, and also some semi-synthetic derivatives of safranal were tested in order to establish which modifications in the chemical structure could improve the biological activity. According to our promising results, we virtually screened our compounds by means of molecular modeling studies against the main H. pylori enzymes in order to unravel their putative mechanism of action.

  10. A carborane-derivative "click" reaction under heterogeneous conditions for the synthesis of a promising lipophilic MRI/GdBNCT agent.

    PubMed

    Toppino, Antonio; Bova, Maria Elena; Geninatti Crich, Simonetta; Alberti, Diego; Diana, Eliano; Barge, Alessandro; Aime, Silvio; Venturello, Paolo; Deagostino, Annamaria

    2013-01-01

    In this study, the Huisgen reaction has been used to functionalise a carborane cage with a lipophilic moiety and a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) ligand to obtain a new Gd boron neutron-capture therapy (BNCT)/magnetic resonance imaging (MRI) agent. The introduction of the triazole units has been accomplished under both heterogeneous conditions, by the use of a Cu-supported ionic-liquid catalyst, and homogeneous conditions. The ability of the Gd complex of the synthesised ligand to form stable adducts with low-density lipoproteins (LDLs) has been evaluated and then MRI has been performed on tumour melanoma cells incubated in the presence of a Gd-complex/LDL imaging probe. It has been concluded that the high amount of intracellular boron necessary to perform BNCT can be reached even in the presence of a relatively low-boron-containing LDL concentration. PMID:23154917

  11. Synthesis, Photophysical, and Biological Evaluation of Sulfated Polyglycerol Dendronized Perylenebisimides (PBIs)--A Promising Platform for Anti-Inflammatory Theranostic Agents?

    PubMed

    Heek, T; Kühne, C; Depner, H; Achazi, K; Dernedde, J; Haag, R

    2016-03-16

    A set of four water-soluble perylene bisimides (PBI) based on sulfated polyglycerol (PGS) dendrons were developed, their photophysical properties determined via UV/vis and fluorescence spectroscopy, and their performance as possible anti-inflammatory agents evaluated via biological in vitro studies. It could be shown that in contrast to charge neutral PG-PBIs the introduction of the additional electrostatic repulsion forces leads to a decrease in the dendron generation necessary for aggregation suppression, allowing the preparation of PBIs with fluorescence quantum yields of >95% with a considerable decreased synthetic effort. Furthermore, the values determined for L-selectin binding down to the nanomolar range, their limited impact on blood coagulation, and their minor activation of the complement system renders these systems ideal for anti-inflammatory purposes. PMID:26890394

  12. Dysregulated Expression of Glycolipids in Tumor Cells: From Negative Modulator of Anti-tumor Immunity to Promising Targets for Developing Therapeutic Agents

    PubMed Central

    Daniotti, Jose Luis; Lardone, Ricardo D.; Vilcaes, Aldo A.

    2016-01-01

    Glycolipids are complex molecules consisting of a ceramide lipid moiety linked to a glycan chain of variable length and structure. Among these are found the gangliosides, which are sialylated glycolipids ubiquitously distributed on the outer layer of vertebrate plasma membranes. Changes in the expression of certain species of gangliosides have been described to occur during cell proliferation, differentiation, and ontogenesis. However, the aberrant and elevated expression of gangliosides has been also observed in different types of cancer cells, thereby promoting tumor survival. Moreover, gangliosides are actively released from the membrane of tumor cells, having a strong impact on impairing anti-tumor immunity. Beyond the undesirable effects of gangliosides in cancer cells, a substantial number of cancer immunotherapies have been developed in recent years that have used gangliosides as the main target. This has resulted in successful immune cell- or antibody-responses against glycolipids, with promising results having been obtained in clinical trials. In this review, we provide a general overview on the metabolism of glycolipids, both in normal and tumor cells, as well as examining glycolipid-mediated immune modulation and the main successes achieved in immunotherapies using gangliosides as molecular targets. PMID:26779443

  13. Pseudomonas aeruginosa cells adapted to benzalkonium chloride show resistance to other membrane-active agents but not to clinically relevant antibiotics.

    PubMed

    Loughlin, M F; Jones, M V; Lambert, P A

    2002-04-01

    Our objective was to determine whether strains of Pseudomonas aeruginosa can adapt to growth in increasing concentrations of the disinfectant benzalkonium chloride (BKC), and whether co-resistance to clinically relevant antimicrobial agents occurs. Attempts were made to determine what phenotypic alterations accompanied resistance and whether these explained the mechanism of resistance. Strains were serially passaged in increasing concentrations of BKC in static nutrient broth cultures. Serotyping and genotyping were used to determine purity of the cultures. Two strains were examined for cross-resistance to other disinfectants and antibiotics by broth dilution MIC determination. Alterations in outer membrane proteins and lipopolysaccharide (LPS) expressed were examined by SDS-PAGE. Cell surface hydrophobicity and charge, uptake of disinfectant and proportion of specific fatty acid content of outer and cytoplasmic membranes were determined. Two P. aeruginosa strains showed a stable increase in resistance to BKC. Co-resistance to other quaternary ammonium compounds was observed in both strains; chloramphenicol and polymyxin B resistance were observed in one and a reduction in resistance to tobramycin observed in the other. However, no increased resistance to other biocides (chlorhexidine, triclosan, thymol) or antibiotics (ceftazidime, imipenem, ciprofloxacin, tobramycin) was detected. Characteristics accompanying resistance included alterations in outer membrane proteins, uptake of BKC, cell surface charge and hydrophobicity, and fatty acid content of the cytoplasmic membrane, although no evidence was found for alterations in LPS. Each of the two strains had different alterations in phenotype, indicating that such adaptation is unique to each strain of P. aeruginosa and does not result from a single mechanism shared by the whole species. PMID:11909837

  14. Ligands for cannabinoid receptors, promising anticancer agents.

    PubMed

    Nikan, Marjan; Nabavi, Seyed Mohammad; Manayi, Azadeh

    2016-02-01

    Cannabinoid compounds are unique to cannabis and provide some interesting biological properties. These compounds along with endocannabinoids, a group of neuromodulator compounds in the body especially in brain, express their effects by activation of G-protein-coupled cannabinoid receptors, CB1 and CB2. There are several physiological properties attributed to the endocannabinoids including pain relief, enhancement of appetite, blood pressure lowering during shock, embryonic development, and blocking of working memory. On the other hand, activation of endocannabinoid system may be suppresses evolution and progression of several types of cancer. According to the results of recent studies, CB receptors are over-expressed in cancer cell lines and application of multiple cannabinoid or cannabis-derived compounds reduce tumor size through decrease of cell proliferation or induction of cell cycle arrest and apoptosis along with desirable effect on decrease of tumor-evoked pain. Therefore, modulation of endocannabinoid system by inhibition of fatty acid amide hydrolase (FAAH), the enzyme, which metabolized endocannabinoids, or application of multiple cannabinoid or cannabis-derived compounds, may be appropriate for the treatment of several cancer subtypes. This review focuses on how cannabinoid affect different types of cancers. PMID:26764235

  15. Coumarin: a promising scaffold for anticancer agents.

    PubMed

    Kaur, Manjinder; Kohli, Swarandeep; Sandhu, Sonali; Bansal, Yogita; Bansal, Gulshan

    2015-01-01

    Coumarin enjoys an important place in drug discovery process due to its presence in diversity of biologically active compounds. Many compounds of plant origin are derivatives of coumarin. Taking these natural products as lead, research groups across the globe have designed and synthesized numerous coumarin analogues for treatment of varied diseases. Cancer is one of the dreadful chronic diseases, and many drugs are available for its treatment. However, due to heterogeneity of cancer, the search is still on to develop drugs for specific types of cancers. The present review is an attempt to study various coumarin derivatives of natural as well as synthetic origins, which are identified or developed for the treatment of different types of cancers. Herein, we have classified various anticancer coumarin derivatives on the basis of their origin as well as substitution around it. These are discussed under the headings of natural, semi-synthetic and synthetic coumarin derivatives. The synthetic coumarin derivatives are further classified as mono-, di- and poly-substituted and fused coumarin derivatives. Of the six positions available for substituents on coumarin nucleus, only three positions (C-3, C-4 and C-7) are exploited for the selection of functional groups appropriate for anticancer activity. The other positions (C-5, C-6 and C-8) are either unexplored or very less exploited. The present review is expected to provide the medicinal chemists a guide to choose new functional groups for substitution at different positions of coumarin nucleus for development of novel compounds for the treatment of a specific type of cancer.

  16. Promising therapeutic targets in neuroblastoma.

    PubMed

    Matthay, Katherine K; George, Rani E; Yu, Alice L

    2012-05-15

    Neuroblastoma, the most common extracranial solid tumor in children, is derived from neural crest cells. Nearly half of patients present with metastatic disease and have a 5-year event-free survival of <50%. New approaches with targeted therapy may improve efficacy without increased toxicity. In this review we evaluate 3 promising targeted therapies: (i) (131)I-metaiodobenzylguanidine (MIBG), a radiopharmaceutical that is taken up by human norepinephrine transporter (hNET), which is expressed in 90% of neuroblastomas; (ii) immunotherapy with monoclonal antibodies targeting the GD2 ganglioside, which is expressed on 98% of neuroblastoma cells; and (iii) inhibitors of anaplastic lymphoma kinase (ALK), a tyrosine kinase that is mutated or amplified in ~10% of neuroblastomas and expressed on the surface of most neuroblastoma cells. Early-phase trials have confirmed the activity of (131)I-MIBG in relapsed neuroblastoma, with response rates of ~30%, but the technical aspects of administering large amounts of radioactivity in young children and limited access to this agent have hindered its incorporation into treatment of newly diagnosed patients. Anti-GD2 antibodies have also shown activity in relapsed disease, and a recent phase III randomized trial showed a significant improvement in event-free survival for patients receiving chimeric anti-GD2 (ch14.18) combined with cytokines and isotretinoin after myeloablative consolidation therapy. A recently approved small-molecule inhibitor of ALK has shown promising preclinical activity for neuroblastoma and is currently in phase I and II trials. This is the first agent directed to a specific mutation in neuroblastoma, and marks a new step toward personalized therapy for neuroblastoma. Further clinical development of targeted treatments offers new hope for children with neuroblastoma.

  17. Antimicrobials for bacterial bioterrorism agents.

    PubMed

    Sarkar-Tyson, Mitali; Atkins, Helen S

    2011-06-01

    The limitations of current antimicrobials for highly virulent pathogens considered as potential bioterrorism agents drives the requirement for new antimicrobials that are suitable for use in populations in the event of a deliberate release. Strategies targeting bacterial virulence offer the potential for new countermeasures to combat bacterial bioterrorism agents, including those active against a broad spectrum of pathogens. Although early in the development of antivirulence approaches, inhibitors of bacterial type III secretion systems and cell division mechanisms show promise for the future.

  18. Promising therapeutic targets in neuroblastoma

    PubMed Central

    Matthay, Katherine K.; George, Rani E.; Yu, Alice L.

    2012-01-01

    Neuroblastoma, the most common extra- cranial solid tumor in children, is derived from neural crest cells. Nearly half of patients present with metastatic disease, and have 5-year EFS of less than 50%. New approaches with targeted therapy may improve efficacy without increased toxicity. The current review will evaluate three promising targeted therapies, including 131I-metaiodobenzylguanidine (MIBG), a radiopharmaceutical taken up by the human norepinephrine transporter expressed in 90% of neuroblastomas, immunotherapy with monoclonal antibodies targeting the GD2 ganglioside, expressed on 98% of neuroblastoma cells, and inhibitors of ALK, a tyrosine kinase which is mutated or amplified in approximately 10% of neuroblastoma and expressed on the surface of most neuroblastoma cells. Early phase trials have confirmed the activity of 131I-MIBG in relapsed neuroblastoma, with response rates of about 30%, but the technical aspects of administration of large amounts of radioactivity in young children and the limited access have hindered incorporation into treatment of newly diagnosed patients. Anti-GD2 antibodies have also demonstrated activity in relapsed disease, and a recent phase III randomized trial showed a significant improvement in event-free survival for patients receiving chimeric anti-GD2 (ch14.18) combined with cytokines and isotretinoin after myeloablative consolidation therapy. A recently approved small molecule inhibitor of ALK has promising pre-clinical activity for neuroblastoma, and is currently in phase I and II trials. This is the first agent directed to a specific mutation in neuroblastoma, and marks a new step toward personalized therapy for neuroblastoma. Further clinical development of targeted treatments offers new hope for children with neuroblastoma. PMID:22589483

  19. Promises, promises for neuroscience and law.

    PubMed

    Buckholtz, Joshua W; Faigman, David L

    2014-09-22

    Stunning technical advances in the ability to image the human brain have provoked excited speculation about the application of neuroscience to other fields. The 'promise' of neuroscience for law has been touted with particular enthusiasm. Here, we contend that this promise elides fundamental conceptual issues that limit the usefulness of neuroscience for law. Recommendations for overcoming these challenges are offered.

  20. Yersinia pseudotuberculosis and Yersinia pestis show increased outer membrane permeability to hydrophobic agents which correlates with lipopolysaccharide acyl-chain fluidity.

    PubMed

    Bengoechea, J A; Brandenburg, K; Seydel, U; Díaz, R; Moriyón, I

    1998-06-01

    The hydrophobic probe N-phenyl-1-naphthylamine accumulated less in non-pathogenic Yersinia spp. and non-pathogenic and pathogenic Yersinia enterocolitica than in Yersinia pseudotuberculosis or Yersinia pestis. This was largely due to differences in the activity of efflux systems, but also to differences in outer membrane permeability because uptake of the probe in KCN/arsenate-poisoned cells was slower in the former group than in Y. pseudotuberculosis and Y. pestis. The probe accumulation rate was higher in Y. pseudotuberculosis and Y. pestis grown at 37 degrees C than at 26 degrees C and was always highest in Y. pestis. These yersiniae had LPSs with shorter polysaccharides than Y. enterocolitica, particularly when grown at 37 degrees C. Gel<-->liquid-crystalline phase transitions (Tc 28-31 degrees C) were observed in LPS aggregates of Y. enterocolitica grown at 26 and 37 degrees C, with no differences between non-pathogenic and pathogenic strains. Y. pseudotuberculosis and Y. pestis LPSs showed no phase transitions and, although the fluidity of LPSs of Y. pseudotuberculosis and Y. enterocolitica grown at 26 degrees C were close below the Tc of the latter, they were always in a more fluid state than Y. enterocolitica LPS. Comparison with previous studies of Salmonella choleraesuis subsp. choleraesuis serotype minnesota rough LPS showed that the increased fluidity and absence of transition of Y. pseudotuberculosis and Y. pestis LPSs cannot be explained by their shorter polysaccharides and suggested differences at the lipid A/core level. It is proposed that differences in LPS-LPS interactions and efflux activity explain the above observations and reflect the adaptation of Yersinia spp. to different habitats.

  1. Breast vibro-acoustography: initial results show promise

    PubMed Central

    2012-01-01

    Introduction Vibro-acoustography (VA) is a recently developed imaging modality that is sensitive to the dynamic characteristics of tissue. It detects low-frequency harmonic vibrations in tissue that are induced by the radiation force of ultrasound. Here, we have investigated applications of VA for in vivo breast imaging. Methods A recently developed combined mammography-VA system for in vivo breast imaging was tested on female volunteers, aged 25 years or older, with suspected breast lesions on their clinical examination. After mammography, a set of VA scans was acquired by the experimental device. In a masked assessment, VA images were evaluated independently by 3 reviewers who identified mass lesions and calcifications. The diagnostic accuracy of this imaging method was determined by comparing the reviewers' responses with clinical data. Results We collected images from 57 participants: 7 were used for training and 48 for evaluation of diagnostic accuracy (images from 2 participants were excluded because of unexpected imaging artifacts). In total, 16 malignant and 32 benign lesions were examined. Specificity for diagnostic accuracy was 94% or higher for all 3 reviewers, but sensitivity varied (69% to 100%). All reviewers were able to detect 97% of masses, but sensitivity for detection of calcification was lower (≤ 72% for all reviewers). Conclusions VA can be used to detect various breast abnormalities, including calcifications and benign and malignant masses, with relatively high specificity. VA technology may lead to a new clinical tool for breast imaging applications. PMID:23021305

  2. Nuclear system that burns its own wastes shows promise

    NASA Technical Reports Server (NTRS)

    Atchison, K.

    1975-01-01

    A nuclear fission energy system, capable of eliminating a significant amount of its radioactive wastes by burning them, is described. A theoretical investigation of this system conducted by computer analysis, is based on use of gaseous fuel nuclear reactors. Gaseous core reactors using a uranium plasma fuel are studied along with development for space propulsion.

  3. New Treatment Shows Promise for Crippling Knee Arthritis

    MedlinePlus

    ... noted Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, in Winston-Salem, N. ... Montpellier, France; Anthony Atala, M.D., director, Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., ...

  4. Monoclonal Antibody Shows Promise as Potential Therapeutic for MERS | Poster

    Cancer.gov

    A monoclonal antibody has proven effective in preventing Middle Eastern Respiratory Syndrome (MERS) in lab animals, suggesting further development as a potential intervention for the deadly disease in humans, according to new research. MERS is a newly emerged coronavirus first detected in humans in 2012. Most cases have occurred in the Middle East, but the disease has appeared elsewhere. In all, MERS has infected more than 1,700 individuals and killed more than 600, according to the World Health Organization. No vaccines or antiviral therapies currently exist. Several candidate vaccines are being developed, and some have been tested in animal models, a prerequisite to human clinical trials.

  5. Cord-Blood Transplants Show Promise in Leukemia Treatment

    MedlinePlus

    ... 7, 2016 WEDNESDAY, Sept. 7, 2016 (HealthDay News) -- Bone marrow or stem cell transplants can save the lives of adults and ... is to find a relative who can donate bone marrow or stem cells, preferably a "matched" sibling whose blood is compatible ...

  6. Uranyl phthalocyanines show promise in the treatment of brain tumors

    NASA Technical Reports Server (NTRS)

    Frigerio, N. A.

    1967-01-01

    Processes synthesize sulfonated and nonsulfonated uranyl phthalocyanines for application in neutron therapy of brain tumors. Tests indicate that the compounds are advantageous over the previously used boron and lithium compounds.

  7. Non-Addictive Painkiller Shows Promise in Animal Trials

    MedlinePlus

    ... The experimental medication "has the potential to replace morphine as the gold standard for treating severe pain," ... such as Percocet (acetaminophen/oxycodone), OxyContin (oxycodone) and morphine, but minus the negative effects, doctors say. The ...

  8. Radial furnace shows promise for growing straight boron carbide whiskers

    NASA Technical Reports Server (NTRS)

    Feingold, E.

    1967-01-01

    Radial furnace, with a long graphite vaporization tube, maintains a uniform thermal gradient, favoring the growth of straight boron carbide whiskers. This concept seems to offer potential for both the quality and yield of whiskers.

  9. Performance-Pay Setup in Texas Shows Promise

    ERIC Educational Resources Information Center

    Honawar, Vaishali; Keller, Bess

    2008-01-01

    Independent studies of the nation's largest performance-pay system suggest that the state-backed plans in Texas could be having positive effects on teacher attitudes, with educators reporting they collaborate more with colleagues and encourage students to work harder than they did before the plans were implemented. Schools participating in the…

  10. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

    Cancer.gov

    Adding the drug everolimus (Afinitor®) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone.

  11. Three-dimensional magnetic resonance cardiac imaging shows initial promise

    SciTech Connect

    Not Available

    1988-04-15

    Three-dimensional magnetic resonance imaging (3-D MRI) of the heart is already receiving encouraging reviews from heart surgeons, says Michael Vannier, MD, an associate professor of radiology at Washington University School of Medicine, St. Louis. In fact, the demand for his group's 3-D images is becoming overwhelming, Vannier says. So far, the group has used 3-D MRI to evaluate congenital heart disease. The advantage of the 3-D system is that, even to an untrained eye, anomalies are apparent and the images can even be animated. Many of the patients are infants, who are sedated while the images are acquired. When the information is combined, the averaged image produced represents a slice about 5 mm thick. The computer then stacks a number of those images together to make the 3-D image. Total scanning takes about one hour.

  12. Credible threats and promises.

    PubMed Central

    McNamara, John M; Houston, Alasdair I

    2002-01-01

    We consider various implications of information about the other player in two-player evolutionary games. A simple model of desertion shows that information about the partner's behaviour can be disadvantageous, and highlights the idea of credible threats. We then discuss the general issue of whether the partner can convince the focal player that it will behave in a specific way, i.e. whether the focal player can make credible threats or promises. We show that when desertion decisions depend on reserves, a player can manipulate its reserves so as to create a credible threat of desertion. We then extend previous work on the evolution of trust and commitment, discussing conditions under which it is advantageous to assume that a partner will behave in a certain way even though it is not in its best interest. PMID:12495517

  13. Developing Mathematically Promising Students.

    ERIC Educational Resources Information Center

    Sheffield, Linda Jensen, Ed.

    This book, written on the recommendation of the Task Force on Mathematically Promising Students, investigates issues involving the development of promising mathematics students. Recommendations are made concerning topics such as the definition of promising students; the identification of such students; appropriate curriculum, instruction, and…

  14. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

    For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the state's best…

  15. The Kalamazoo Promise Scholarship

    ERIC Educational Resources Information Center

    Bartik, Timothy J.; Lachowska, Marta

    2014-01-01

    This study takes advantage of the unexpected announcement of the Kalamazoo Promise to study its effects on student achievement and behavior in high school. The Kalamazoo Promise provides college scholarships to graduates of Kalamazoo Public Schools (KPS), a midsized urban school district in Michigan that is racially and economically diverse.…

  16. Keeping the Promise

    ERIC Educational Resources Information Center

    Whissemore, Tabitha

    2016-01-01

    Since its launch in September 2015, Heads Up America has collected information on nearly 125 promise programs across the country, many of which were instituted long before President Barack Obama announced the America's College Promise (ACP) plan in 2015. At least 27 new free community college programs have launched in states, communities, and at…

  17. Progress and promise.

    PubMed

    Kamphaus, Randy W

    2012-12-01

    This editorial introduces the current issue of the journal School Psychology Quarterly (SPQ).There has been an impressive and promising progress of school psychology science has been reflected in every issue of SPQ, including the current one.

  18. PROMISE. Beyond frontiers.

    PubMed

    Ray, Manaan Kar; Rae, Sarah; Agius, Mark

    2015-09-01

    The concepts underlying the PROMISE initiative are described. This initiative to implement more humane healthcare is now developing from a local initiativein Cambridge to a global movement. PMID:26417826

  19. The putative role of lutein and zeaxanthin as protective agents against age-related macular degeneration: promise of molecular genetics for guiding mechanistic and translational research in the field1234

    PubMed Central

    Neuringer, Martha

    2012-01-01

    Age-related macular degeneration (AMD) is the primary cause of vision loss in elderly people of western European ancestry. Genetic, dietary, and environmental factors affect tissue concentrations of macular xanthophylls (MXs) within retinal cell types manifesting AMD pathology. In this article we review the history and state of science on the putative role of the MXs (lutein, zeaxanthin, and meso-zeaxanthin) in AMD and report findings on AMD-associated genes encoding enzymes, transporters, ligands, and receptors affecting or affected by MXs. We then use this context to discuss emerging research opportunities that offer promise for meaningful investigation and inference in the field. PMID:23053548

  20. Ring fusion strategy for synthesis and lead optimization of sulfur-substituted anthra[1,2-c][1,2,5]thiadiazole-6,11-dione derivatives as promising scaffold of antitumor agents.

    PubMed

    Lee, Yu-Ru; Chen, Tsung-Chih; Lee, Chia-Chung; Chen, Chun-Liang; Ahmed Ali, Ahmed Atef; Tikhomirov, Alexander; Guh, Jih-Hwa; Yu, Dah-Shyong; Huang, Hsu-Shan

    2015-09-18

    A series of sulfur-substituted anthra[1,2-c][1,2,5]thiadiazole-6,11-diones were synthesized and evaluated using the cell proliferations, apoptosis and NCI-60 cell panel assays. Also, the signaling pathways that account for their activities were investigated. Compounds 2, 3, 4a, 4d, 4f, 4i, 4k, 5b, 5c, 5d, 5f, 5g, 6b, 6c, 6d, 6e, 6g, 7a and 7g were selected by NCI. Among the tested compounds, 6g appeared to be the most active compound of this series that not only induced apoptosis in DU-145 cancer cells but also attenuated the ERK1/2 and p38 signaling pathways. All test compounds exhibited diverse cytostatic and cytotoxic activities that warrant further development as potential anticancer agents.

  1. Promising More Information

    NASA Technical Reports Server (NTRS)

    2003-01-01

    When NASA needed a real-time, online database system capable of tracking documentation changes in its propulsion test facilities, engineers at Stennis Space Center joined with ECT International, of Brookfield, Wisconsin, to create a solution. Through NASA's Dual-Use Program, ECT developed Exdata, a software program that works within the company's existing Promise software. Exdata not only satisfied NASA s requirements, but also expanded ECT s commercial product line. Promise, ECT s primary product, is an intelligent software program with specialized functions for designing and documenting electrical control systems. An addon to AutoCAD software, Promis e generates control system schematics, panel layouts, bills of material, wire lists, and terminal plans. The drawing functions include symbol libraries, macros, and automatic line breaking. Primary Promise customers include manufacturing companies, utilities, and other organizations with complex processes to control.

  2. Spacecraft sanitation agent development

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The development of an effective sanitizing agent that is compatible with the spacecraft environment and the human occupant is discussed. Experimental results show that two sanitation agents must be used to satisfy mission requirements: one agent for personal hygiene and one for equipment maintenance. It was also recommended that a water rinse be used with the agents for best results, and that consideration be given to using the agents pressure packed or in aerosol formulations.

  3. Inferences from counterfactual threats and promises.

    PubMed

    Egan, Suzanne M; Byrne, Ruth M J

    2012-01-01

    We examine how people understand and reason from counterfactual threats, for example, "if you had hit your sister, I would have grounded you" and counterfactual promises, for example, "if you had tidied your room, I would have given you ice-cream." The first experiment shows that people consider counterfactual threats, but not counterfactual promises, to have the illocutionary force of an inducement. They also make the immediate inference that the action mentioned in the "if" part of the counterfactual threat and promise did not occur. The second experiment shows that people make more negative inferences (modus tollens and denial of the antecedent) than affirmative inferences (modus ponens and affirmation of the consequent) from counterfactual threats and promises, unlike indicative threats and promises. We discuss the implications of the results for theories of the mental representations and cognitive processes that underlie conditional inducements. PMID:22580411

  4. Oxidative stress and the unfulfilled promises of antioxidant agents

    PubMed Central

    Giorgio, Marco

    2015-01-01

    It is well known that aging and its associated diseases, including cancer, are triggered by oxidative damage to biological macromolecules. However, antioxidant compounds are still disappointingly distant from any clinical application, so that Jim Watson has declared that antioxidant supplementation may have caused more cancers than it has prevented Watson J ((2013) Oxidants, antioxidants and the current incurability of metastatic cancers Open Biol 3 DOI: 10.1098/rsob.120144). To clarify this paradox, here, we describe the mechanisms of oxidative stress focusing in particular on redox balance and physiological oxidative signals. PMID:26284120

  5. Beta-carboline-3-carboxamide derivatives as promising antileishmanial agents

    PubMed Central

    Pedroso, R B; Tonin, L T D; Ueda-Nakamura, T; Filho, B P Dias; Sarragiotto, M H; Nakamura, C V

    2011-01-01

    Leishmaniasis has an overwhelming impact on global public health especially in tropical and subtropical countries and the currently available antileishmanial drugs have serious side effects and low efficacy. Natural and synthetic compounds have been tested in the past few years against Leishmania and the beta-carboline class of compounds have shown great results in antiparasitic chemotherapy. In the present study, three 1-substituted beta-carboline-3-carboxamides (3–5) and 1-substituted beta-carboline-3-carboxylic acid (2) were synthesized and screened for in vitro activity against L. amazonensis. Compound 5 (N-benzyl 1-(4-methoxy)phenyl-9H-beta-carboline-3-carboxamide) had the best activity against promastigote and axenic amastigote forms with IC50 of 2.6 and 1.0 μM, respectively. Its CC50 on macrophages cell line was higher than 2457.0 μM with an SI ratio of 930.2. Against intracellular amastigote forms, it had a dose-dependent relationship with a 50% growth inhibitory concentration of 1.0 μM. Through morphological and ultrastructure analysis of promastigote forms treated with compound 5, alterations on cell shape and number of flagella and nuclear membrane damage were observed. For this, compound 5 supports the idea for more in vitro and in vivo studies. PMID:22325814

  6. Natural compounds as anticancer agents: Experimental evidence

    PubMed Central

    Wang, Jiao; Jiang, Yang-Fu

    2012-01-01

    Cancer prevention research has drawn much attention worldwide. It is believed that some types of cancer can be prevented by following a healthy life style. Cancer chemoprevention by either natural or synthetic agents is a promising route towards lowering cancer incidence. In recent years, the concept of cancer chemoprevention has evolved greatly. Experimental studies in animal models demonstrate that the reversal or suppression of premalignant lesions by chemopreventive agents is achievable. Natural occurring agents such as dietary phytochemicals, tea polyphenols and resveratrol show chemopreventive activity in animal models. Moreover, clinical trials for testing the safety and efficacy of a variety of natural agents in preventing or treating human malignancy have been ongoing. Here, we summarize experimental data on the chemopreventive or tumor suppressive effects of several natural compounds including curcumin, (-)-epigallocatechin-3-gallate, resveratrol, indole-3-carbinol, and vitamin D. PMID:24520533

  7. The promise of psychiatric pharmacogenomics.

    PubMed

    Hamilton, Steven P

    2015-01-01

    Clinicians already face "personalized" medicine every day while experiencing the great variation in toxicities and drug efficacy among individual patients. Pharmacogenetics studies are the platform for discovering the DNA determinants of variability in drug response and tolerability. Research now focuses on the genome after its beginning with analyses of single genes. Therapeutic outcomes from several psychotropic drugs have been weakly linked to specific genetic variants without independent replication. Drug side effects show stronger associations to genetic variants, including human leukocyte antigen loci with carbamazepine-induced dermatologic outcome and MC4R with atypical antipsychotic weight gain. Clinical implementation has proven challenging, with barriers including a lack of replicable prospective evidence for clinical utility required for altering medical care. More recent studies show promising approaches for reducing these barriers to routine incorporation of pharmacogenetics data into clinical care.

  8. Diamine curing agents for polyurethanes

    NASA Technical Reports Server (NTRS)

    Bell, V. L.; St. Clair, T. L.

    1975-01-01

    Three aromatic diamines have properties that make them promising candidates as curing agents for converting isocyanates to polyurethanes with higher adhesive strengths, higher softening temperatures, better toughness, and improved abrasion resistance.

  9. Agent Orange

    MedlinePlus

    ... Index Agent Orange Agent Orange Home Facts about Herbicides Veterans' Diseases Birth Defects Benefits Exposure Locations Provider ... millions of gallons of Agent Orange and other herbicides on trees and vegetation during the Vietnam War. ...

  10. Adaptive management: Promises and pitfalls

    NASA Astrophysics Data System (ADS)

    McLain, Rebecca J.; Lee, Robert G.

    1996-07-01

    Proponents of the scientific adaptive management approach argue that it increases knowledge acquisition rates, enhances information flow among policy actors, and provides opportunities for creating shared understandings. However, evidence from efforts to implement the approach in New Brunswick, British Columbia, Canada, and the Columbia River Basin indicates that these promises have not been met. The data show that scientific adaptive management relies excessively on the use of linear systems models, discounts nonscientific forms of knowledge, and pays inadequate attention to policy processes that promote the development of shared understandings among diverse stakeholders. To be effective, new adaptive management efforts will need to incorporate knowledge from multiple sources, make use of multiple systems models, and support new forms of cooperation among stakeholders.

  11. Bioavailability of quercetin: problems and promises.

    PubMed

    Cai, X; Fang, Z; Dou, J; Yu, A; Zhai, G

    2013-01-01

    Quercetin (QC) is a typical plant flavonoid, possesses diverse pharmacologic effects including antiinflammatory, antioxidant, anti-cancer, anti-anaphylaxis effects and against aging. However, the application of QC in pharmaceutical field is limited due to its poor solubility, low bioavailability, poor permeability and instability. To improve the bioavailability of QC, numerous approaches have been undertaken, involving the use of promising drug delivery systems such as inclusion complexes, liposomes, nanoparticles or micelles, which appear to provide higher solubility and bioavailability. Enhanced bioavailability of QC in the near future is likely to bring this product to the forefront of therapeutic agents for treatment of human disease.

  12. The Ambivalence of Promising Technology

    PubMed Central

    2010-01-01

    Issues of responsibility in the world of nanotechnology are becoming explicit with the emergence of a discourse on ‘responsible development’ of nanoscience and nanotechnologies. Much of this discourse centres on the ambivalences of nanotechnology and of promising technology in general. Actors must find means of dealing with these ambivalences. Actors’ actions and responses to ambivalence are shaped by their position and context, along with strategic games they are involved in, together with other actors. A number of interviews were conducted with industrial actors with the aim of uncovering their ethical stances towards responsible development of nanotechnology. The data shows that standard repertoires of justification of nanotechnological development were used. Thus, the industrial actors fell back on their position and associated responsibilities. Such responses reinforce a division of moral labour in which industrial actors and scientists can focus on the progress of science and technology, while other actors, such as NGOs, are expected to take care of broader considerations, such as ethical and social issues. PMID:20835398

  13. Biological Agents

    MedlinePlus

    ... to Z Index Contact Us FAQs What's New Biological Agents This page requires that javascript be enabled ... and Health Topics A-Z Index What's New Biological agents include bacteria, viruses, fungi, other microorganisms and ...

  14. Nanotechnology: Its Promise and Challenges

    SciTech Connect

    Vicki Colvin

    2009-05-14

    Vicki Colvin of Rice University talks about how nanotechnology-enabled systems, with dimensions on the scale of a billionth of a meter, offer great promise for solving difficult social problems and creating enormous possibilities.

  15. Promising Practices: Vocational Education Resource Package.

    ERIC Educational Resources Information Center

    Evaluation and Training Inst., Los Angeles, CA.

    Developed to assist community college administrators and faculty in enhancing vocational educational programs and services, this Vocational Education Resource Package profiles four vocational education programs at California community colleges that show promise in serving special population students. First, the Applied Mathematics for Electronics…

  16. Broad-spectrum antiviral agents

    PubMed Central

    Zhu, Jun-Da; Meng, Wen; Wang, Xiao-Jia; Wang, Hwa-Chain R.

    2015-01-01

    Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents. PMID:26052325

  17. "A Promise Kept, a Promise Broken": Developmental Bases of Trust.

    ERIC Educational Resources Information Center

    Rotenberg, Ken J.

    1980-01-01

    Sixteen children from each of kindergarten, second, and fourth grades were presented pictorially and verbally with a series of stories depicting actors who varied in the amount of helping they promised to do and in whether or not they helped. Findings indicated developmental change in the bases of trust. (RH)

  18. Antimicrobial peptides: premises and promises.

    PubMed

    Reddy, K V R; Yedery, R D; Aranha, C

    2004-12-01

    Antimicrobial peptides (AMPs) are an important component of the natural defences of most living organisms against invading pathogens. These are relatively small (< 10kDa), cationic and amphipathic peptides of variable length, sequence and structure. During the past two decades several AMPs have been isolated from a wide variety of animals, both vertebrates and invertebrates, and plants as well as from bacteria and fungi. Most of these peptides are obtained from different sources like macrophages, neutrophils, epithelial cells, haemocytes, fat body, reproductive tract, etc. These peptides exhibit broad-spectrum activity against a wide range of microorganisms including Gram-positive and Gram-negative bacteria, protozoa, yeast, fungi and viruses. A few peptides have also been found to be cytotoxic to sperm and tumour cells. AMPs are classified based on the three dimensional structural studies carried out with the help of NMR. The peptides are broadly classified into five major groups namely (a) peptides that form alpha-helical structures, (b) peptides rich in cysteine residues, (c) peptides that form beta-sheet, (d) peptides rich in regular amino acids namely histatin, arginine and proline and (e) peptides composed of rare and modified amino acids. Most of these peptides are believed to act by disrupting the plasma membrane leading to the lysis of the cell. AMPs have been found to be excellent candidates for developing novel antimicrobial agents and a few of these peptides show antimicrobial activity against pathogens causing sexually transmitted infection (STI), including HIV/HSV. Peptides, namely magainin and nisin have been shown to demonstrate contraceptive properties in vitro and in vivo. A few peptides have already entered clinical trials for the treatment of impetigo, diabetic foot ulcers and gastric helicobacter infections. In this review, we discuss the source, structures and mode of action with special reference to therapeutic considerations of various AMPs

  19. 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. PMID:27112322

  20. Glycodendritic structures: promising new antiviral drugs.

    PubMed

    Rojo, Javier; Delgado, Rafael

    2004-09-01

    DC-SIGN, a C-type lectin expressed by dendritic cells, is able to recognize high mannosylated glycoproteins at the surface of a broad range of pathogens including viruses, bacteria, fungi and parasites. For at least some of these agents this interaction appears to be an important part of the infection process. Therefore, this lectin might be considered in the design of new antiviral drugs. In this manner, multivalent carbohydrate systems based on dendrimers and dendritic polymers are promising candidates as antiviral drugs. Boltorn hyperbranched dendritic polymers functionalized with mannose have been used to inhibit DC-SIGN-mediated infection in an Ebola-pseudotyped viral model. Their physiological solubility, lack of toxicity and especially their low price suggest the application of these glycodendritic polymers for possible formulation as microbicides. PMID:15308605

  1. Taxanes: promising anti-cancer drugs.

    PubMed

    Fauzee, Nilufer Jasmine Selimah

    2011-01-01

    Taxanes are amongst the most promising antitumor agents available at hand today, of increasing importance in Asia given that cancer is now one of the major public health problems which needs to be dealt urgently for the benefit of affected patients. Several ongoing experimental and clinical trials have supported the fact that even with their side effects and poor solubilities, taxanes are still the first lines of treatment chosen for breast, ovary, lung and other metastatic cancers. Prolonging the life of cancer patients is the main aim of all researchers, scientists, pharmaceutical companies and clinicians; therefore this review emphasizes the mechanisms of action of taxanes and how they can play an important role in palliative treatment if not applied for curative purposes, hence being considered a boon for cancer management.

  2. Glycodendritic structures: promising new antiviral drugs.

    PubMed

    Rojo, Javier; Delgado, Rafael

    2004-09-01

    DC-SIGN, a C-type lectin expressed by dendritic cells, is able to recognize high mannosylated glycoproteins at the surface of a broad range of pathogens including viruses, bacteria, fungi and parasites. For at least some of these agents this interaction appears to be an important part of the infection process. Therefore, this lectin might be considered in the design of new antiviral drugs. In this manner, multivalent carbohydrate systems based on dendrimers and dendritic polymers are promising candidates as antiviral drugs. Boltorn hyperbranched dendritic polymers functionalized with mannose have been used to inhibit DC-SIGN-mediated infection in an Ebola-pseudotyped viral model. Their physiological solubility, lack of toxicity and especially their low price suggest the application of these glycodendritic polymers for possible formulation as microbicides.

  3. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous

  4. Agent Architectures for Compliance

    NASA Astrophysics Data System (ADS)

    Burgemeestre, Brigitte; Hulstijn, Joris; Tan, Yao-Hua

    A Normative Multi-Agent System consists of autonomous agents who must comply with social norms. Different kinds of norms make different assumptions about the cognitive architecture of the agents. For example, a principle-based norm assumes that agents can reflect upon the consequences of their actions; a rule-based formulation only assumes that agents can avoid violations. In this paper we present several cognitive agent architectures for self-monitoring and compliance. We show how different assumptions about the cognitive architecture lead to different information needs when assessing compliance. The approach is validated with a case study of horizontal monitoring, an approach to corporate tax auditing recently introduced by the Dutch Customs and Tax Authority.

  5. America: No Promise Without Agony.

    ERIC Educational Resources Information Center

    Brown, Robert McAfee

    We may discover signs of promise in the midst of agony if we make some shifts of perspective. (1) "Our fear of overt violence must be countered by our acknowledgement of covert violence." Covert violence is subtle and more destructive than physical violence because it is the "denial of personhood"--the insinuation by an act or by neglect that a…

  6. Promising Electric Aircraft Drive Systems

    NASA Technical Reports Server (NTRS)

    Dudley, Michael R.

    2010-01-01

    An overview of electric aircraft propulsion technology performance thresholds for key power system components is presented. A weight comparison of electric drive systems with equivalent total delivered energy is made to help identify component performance requirements, and promising research and development opportunities.

  7. The promise of quantum simulation

    DOE PAGES

    Muller, Richard P.; Blume-Kohout, Robin

    2015-07-21

    In this study, quantum simulations promise to be one of the primary applications of quantum computers, should one be constructed. This article briefly summarizes the history of quantum simulation in light of the recent result of Wang and co-workers, demonstrating calculation of the ground and excited states for a HeH+ molecule, and concludes with a discussion of why this and other recent progress in the field suggest that quantum simulations of quantum chemistry have a bright future.

  8. The promise of quantum simulation

    SciTech Connect

    Muller, Richard P.; Blume-Kohout, Robin

    2015-07-21

    In this study, quantum simulations promise to be one of the primary applications of quantum computers, should one be constructed. This article briefly summarizes the history of quantum simulation in light of the recent result of Wang and co-workers, demonstrating calculation of the ground and excited states for a HeH+ molecule, and concludes with a discussion of why this and other recent progress in the field suggest that quantum simulations of quantum chemistry have a bright future.

  9. Cooperation and Coordination Between Fuzzy Reinforcement Learning Agents in Continuous State Partially Observable Markov Decision Processes

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.; Vengerov, David

    1999-01-01

    Successful operations of future multi-agent intelligent systems require efficient cooperation schemes between agents sharing learning experiences. We consider a pseudo-realistic world in which one or more opportunities appear and disappear in random locations. Agents use fuzzy reinforcement learning to learn which opportunities are most worthy of pursuing based on their promise rewards, expected lifetimes, path lengths and expected path costs. We show that this world is partially observable because the history of an agent influences the distribution of its future states. We consider a cooperation mechanism in which agents share experience by using and-updating one joint behavior policy. We also implement a coordination mechanism for allocating opportunities to different agents in the same world. Our results demonstrate that K cooperative agents each learning in a separate world over N time steps outperform K independent agents each learning in a separate world over K*N time steps, with this result becoming more pronounced as the degree of partial observability in the environment increases. We also show that cooperation between agents learning in the same world decreases performance with respect to independent agents. Since cooperation reduces diversity between agents, we conclude that diversity is a key parameter in the trade off between maximizing utility from cooperation when diversity is low and maximizing utility from competitive coordination when diversity is high.

  10. Sulfonamides as multifunctional agents for Alzheimer's disease.

    PubMed

    Bag, Seema; Tulsan, Rekha; Sood, Abha; Cho, Hyejin; Redjeb, Hana; Zhou, Weihong; LeVine, Harry; Török, Béla; Török, Marianna

    2015-02-01

    Sulfonamide linker-based inhibitors with extended linear structure were designed and synthesized with the aim of producing multifunctional agents against several processes involved in the pathology of Alzheimer's disease (AD). The potency of the compounds were assessed in the inhibition of Aβ self-assembly (fibril and oligomer formation), in modulating cholinesterase (AChE, BuChE) activity, and scavenging free radicals. Several compounds exhibited promising Aβ self-assembly and cholinesterase inhibition and in parallel, showed good free radical scavenging properties. The investigation of the scaffold described in this study resulted in the identification of three compounds (14, 19 and 26) as promising leads for the further design of multifunctional drug candidates for AD.

  11. Immunotherapy for advanced melanoma: fulfilling the promise.

    PubMed

    Gogas, Helen; Polyzos, Aristidis; Kirkwood, John

    2013-12-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past thirty years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimes failed to show significant improvement in overall survival. Recent advances and in-depth understanding of the biology of melanoma, have contributed in the development of new agents. Based on the molecular and immunological background of the disease, the new drugs have shown benefit in overall and progression free survival. As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:23725878

  12. Vasoactive agents for the treatment of sepsis

    PubMed Central

    Chen, Kun

    2016-01-01

    The article describes some commonly used vasoactive agents in patients with septic shock. Depending on their distinct pharmacological properties, their effects on vascular bed and cardiac function are different. For example, dopamine has equivalent effect on heart and vasculature, which can result in increases in cardiac output, mean arterial pressure and heart rate. Dobutamine is considered as inodilator because it has potent effect on cardiac systole and vasculature. Patients with sepsis and septic shock sometimes have coexisting cardiac dysfunction that justifies the use of dobutamine. Levosimendan is a relatively new agent exerting its inodilator effect by increasing sensitivity of myocardium to calcium. Some preliminary studies showed a promising result of levosimendan on reducing mortality. PMID:27713891

  13. Nickel-silver composition shows promise as catalyst for hydrogen-oxygen fuel cells

    NASA Technical Reports Server (NTRS)

    Magerl, J. A.; Murray, J. N.

    1970-01-01

    Carburized 3-1 nickel-silver preparation exhibits considerable catalytic activity, although not as high as platinum black. Cost and availability factors warrant further evaluation of nickel-silver materials.

  14. Animation shows promise in initiating timely cardiopulmonary resuscitation: results of a pilot study.

    PubMed

    Attin, Mina; Winslow, Katheryn; Smith, Tyler

    2014-04-01

    Delayed responses during cardiac arrest are common. Timely interventions during cardiac arrest have a direct impact on patient survival. Integration of technology in nursing education is crucial to enhance teaching effectiveness. The goal of this study was to investigate the effect of animation on nursing students' response time to cardiac arrest, including initiation of timely chest compression. Nursing students were randomized into experimental and control groups prior to practicing in a high-fidelity simulation laboratory. The experimental group was educated, by discussion and animation, about the importance of starting cardiopulmonary resuscitation upon recognizing an unresponsive patient. Afterward, a discussion session allowed students in the experimental group to gain more in-depth knowledge about the most recent changes in the cardiac resuscitation guidelines from the American Heart Association. A linear mixed model was run to investigate differences in time of response between the experimental and control groups while controlling for differences in those with additional degrees, prior code experience, and basic life support certification. The experimental group had a faster response time compared with the control group and initiated timely cardiopulmonary resuscitation upon recognition of deteriorating conditions (P < .0001). The results demonstrated the efficacy of combined teaching modalities for timely cardiopulmonary resuscitation. Providing opportunities for repetitious practice when a patient's condition is deteriorating is crucial for teaching safe practice.

  15. Particulate Titanium Matrix Composites Tested-Show Promise for Space Propulsion Applications

    NASA Technical Reports Server (NTRS)

    Thesken, John C.; Lerch, Bradley A.; Arnold, Steven M.

    2003-01-01

    New manufacturing technologies can now produce uniformly distributed particle strengthened titanium matrix composites (TMCs) at lower cost than many types of continuous-fiber composites. The innovative process results in near-final-shape components having a material stiffness up to 26-percent greater than that of components made with conventional titanium materials. This benefit is achieved with no significant increase in the weight of the component. The improved mechanical performance and low-cost manufacturing capability motivated a review of particulate-reinforced metal composite technology as a way to lower the cost and weight of space-access propulsion systems. Focusing on the elevated-temperature properties of titanium alloy Ti-6Al-4V as the matrix material, researchers at the NASA Glenn Research Center conducted experiments to verify the improved performance of the alloy containing 10 wt% of ceramic titanium carbide (TiC) particles. The appropriate blend of metal and ceramic powder underwent a series of cold and hot isostatic pressing procedures to yield bar stock. A set of round dogbone specimens was manufactured from a small sample of the bars. The TMC material proved to have good machinability at this particle concentration as there was no difficulty in producing high-quality specimens.

  16. Editorial Commentary: Iliotibial Band Allograft Shows Promise for Arthroscopic Hip Labral Reconstruction.

    PubMed

    Rossi, Michael J

    2016-01-01

    Arthroscopic hip labral reconstruction using iliotibial band allograft in a modified front-to-back technique results in improved outcomes after 2-year follow-up. The authors' reasoning for reconstruction are reminiscent of similar arguments for restoring hoop stresses in knee meniscal surgery. Results are comparable to reported outcomes of labral repair, and allograft is particularly indicated for severe labral damage when repair is not possible. Don't miss the related technical note with video in Arthroscopy Techniques.

  17. Editorial Commentary: Iliotibial Band Allograft Shows Promise for Arthroscopic Hip Labral Reconstruction.

    PubMed

    Rossi, Michael J

    2016-01-01

    Arthroscopic hip labral reconstruction using iliotibial band allograft in a modified front-to-back technique results in improved outcomes after 2-year follow-up. The authors' reasoning for reconstruction are reminiscent of similar arguments for restoring hoop stresses in knee meniscal surgery. Results are comparable to reported outcomes of labral repair, and allograft is particularly indicated for severe labral damage when repair is not possible. Don't miss the related technical note with video in Arthroscopy Techniques. PMID:26743407

  18. "Signs of Suicide" shows promise as a middle school suicide prevention program.

    PubMed

    Schilling, Elizabeth A; Lawless, Martha; Buchanan, Laurel; Aseltine, Robert H

    2014-12-01

    Although the Signs of Suicide (SOS) suicide prevention program has been implemented at both the middle and high school levels, its efficacy has been demonstrated previously only among high school students. The current study evaluated SOS implemented in high military impact middle schools. Compared to controls, SOS participants demonstrated improved knowledge about suicide and suicide prevention, and participants with pretest ideation reported fewer suicidal behaviors at posttest than controls with pretest ideation. These results provide preliminary evidence for SOS's efficacy as a suicide prevention program for middle school students.

  19. Breeding for improved potato nutrition: High amylose starch potatoes show promise as fiber source

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potato starch is composed of approximately 75% amylopectin and 25% amylose. We are interested in breeding for higher amylose content, which would increase the fiber content of potato and decrease glycemic index. In order to make progress in a breeding program, we have developed a high throughput ass...

  20. Ascension health's demonstration of full disclosure protocol for unexpected events during labor and delivery shows promise.

    PubMed

    Hendrich, Ann; McCoy, Christine Kocot; Gale, Jane; Sparkman, Lora; Santos, Palmira

    2014-01-01

    Communicating openly and honestly with patients and families about unexpected medical events-a policy known as full disclosure-improves outcomes for patients and providers. Although many certification and licensing organizations have declared full disclosure to be imperative, the adoption of and adherence to a full disclosure protocol is not common practice in most clinical settings. We conducted a case study of Ascension Health's implementation of a full disclosure protocol at five labor and delivery demonstration sites. Twenty-seven months after implementation, the rate of full disclosure had increased by 221 percent. Practitioners saw insurers' acceptance of the full disclosure protocol, consistent and ongoing leadership by local practitioners and hospitals, the establishment of a well-trained local investigation and disclosure team, and disclosure training for practitioners as key catalysts for change. Lessons learned from this multisite initiative can inform liability insurers and guide providers who are committed to ensuring that full disclosure becomes the only response to unexpected medical events.

  1. The Promise of Preschool: Local California Efforts Show the Potential of a Statewide Preschool System

    ERIC Educational Resources Information Center

    Perez, Giannina

    2006-01-01

    Tens of thousands of California's 4-year-olds are not enrolled in preschool, ranking California 37th in the nation in preschool enrollment. Pioneering communities throughout the state are working to meet the demand for preschool in their neighborhoods. The achievements of these innovative local efforts indicate the future success of a statewide…

  2. Multilevel Interventions To Address Health Disparities Show Promise In Improving Population Health.

    PubMed

    Paskett, Electra; Thompson, Beti; Ammerman, Alice S; Ortega, Alexander N; Marsteller, Jill; Richardson, DeJuran

    2016-08-01

    Multilevel interventions are those that affect at least two levels of influence-for example, the patient and the health care provider. They can be experimental designs or natural experiments caused by changes in policy, such as the implementation of the Affordable Care Act or local policies. Measuring the effects of multilevel interventions is challenging, because they allow for interaction among levels, and the impact of each intervention must be assessed and translated into practice. We discuss how two projects from the National Institutes of Health's Centers for Population Health and Health Disparities used multilevel interventions to reduce health disparities. The interventions, which focused on the uptake of the human papillomavirus vaccine and community-level dietary change, had mixed results. The design and implementation of multilevel interventions are facilitated by input from the community, and more advanced methods and measures are needed to evaluate the impact of the various levels and components of such interventions. PMID:27503968

  3. Thidiazuron, a non-metablized cytokinin, shows promise in extending the life of potted plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Application of low concentrations of thidiazuron (N-phenyl-N’-1,2,3-thiadiazol-5-yl urea, TDZ) has been shown to be a very effective means of delaying leaf yellowing in cut flowers such as alstroemeria, stock, lilies and tulips. We examined the possible use of this compound for delaying leaf yellow...

  4. Mastering a mediator: blockade of CCN-2 shows early promise in human diabetic kidney disease

    PubMed Central

    2010-01-01

    In diabetes complications, CCN-2 (known originally as CTGF) has been implicated in diabetic nephropathy both as a marker and a mediator of disease. This commentary addresses CCN-2 in diabetic nephropathy, in the context of the recent publication of the first human study to inhibit CCN-2 bioactivity in diabetic kidney disease. PMID:21234125

  5. Surfactants as blackbird stressing agents

    USGS Publications Warehouse

    Lefebvre, P.W.; Seubert, J.L.

    1970-01-01

    Applications of wetting-agent solutions produce mortality in birds. The exact cause of death is undetermined but it is believed that destruction of the insulating qualities of the plumage permits ambient cold temperatures and evaporation to lower the body temperature to a lethal level. The original concept of using these materials as bird-control tools was developed in 1958 at the Patuxent Wildlife Research Center, Bureau of Sport Fisheries and Wildlife Laurel, Maryland. Early field trials by personnel of the Division of Wildlife Services and the Denver Wildlife Research Center indicated that ground-application techniques had promise but limitations of the equipment precluded successful large-scale roost treatments. In 1966, Patuxent Center personnel began using tanker-type aircraft to evaluate high-volume aerial applications of wetting agents. The success of these tests led to the use of small aircraft to make low-volume, high-concentration aerial applications just prior to expected rainfall. Recent trials of the low-volume method show that, with some limitations, it is effective, inexpensive, and safe to the environment. Current research emphasizes the screening of new candidate materials for efficacy, biodegradability, and toxicity to plants and non-target animals, as well as basic investigations of the avian physiological mechanisms involved. Field trials to develop more effective application techniques will continue.

  6. [STEROIDAL GENINS AND GLYCOSIDES OF SPIROSTAN AND FUROSTAN SERIES AS ANTHELMINTHIC AGENTS].

    PubMed

    Islamova, Zh I; Khushbaktova, Z A; Abdullaev, N D; Syrov, V N

    2016-01-01

    It was established that steroidal genins and their glycosides of the spirostan series and (especially) furostan series show anticestodal activity against Hymeiolepis nana species. Search for anthelminthic agents in the indicated series of compounds is a promising direction of research. PMID:27455578

  7. New drugs for medullary thyroid cancer: new promises?

    PubMed

    Spitzweg, Christine; Morris, John C; Bible, Keith C

    2016-06-01

    Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized MTC have had a poor prognosis, partly due to limited response to conventional chemotherapy and radiation therapy. In the past decade, however, considerable progress has been made in identifying key genetic alterations and dysregulated signaling pathways paving the way for the evaluation of a series of multitargeted kinase inhibitors that have started to meaningfully impact clinical practice. Two drugs, vandetanib and cabozantinib, are now approved in the US and EU for use in advanced, progressive MTC, with additional targeted agents also showing promise or awaiting results from clinical trials. However, the potential for toxicities with significant reduction in quality of life and lack of curative outcomes has to be carefully weighed against potential for benefit. Despite significant PFS prolongation observed in randomized clinical trials, most patients even with metastatic disease enjoy indolent courses with slow progression observed over years, wherein watchful waiting is still the preferred strategy. As advanced, progressive MTC is a rare and complex disease, a multidisciplinary approach centered in specialized centers providing interdisciplinary expertise in the individualization of available therapeutic options is preferred. In this review, we summarize current concepts of the molecular pathogenesis of advanced MTC and discuss results from clinical trials of targeted agents and also cytotoxic chemotherapy in the context of clinical implications and future perspectives. PMID:27185870

  8. Chemical Exchange Saturation Transfer (CEST) Agents: Quantum Chemistry and MRI.

    PubMed

    Li, Jikun; Feng, Xinxin; Zhu, Wei; Oskolkov, Nikita; Zhou, Tianhui; Kim, Boo Kyung; Baig, Noman; McMahon, Michael T; Oldfield, Eric

    2016-01-01

    Diamagnetic chemical exchange saturation transfer (CEST) contrast agents offer an alternative to Gd(3+) -based contrast agents for MRI. They are characterized by containing protons that can rapidly exchange with water and it is advantageous to have these protons resonate in a spectral window that is far removed from water. Herein, we report the first results of DFT calculations of the (1) H nuclear magnetic shieldings in 41 CEST agents, finding that the experimental shifts can be well predicted (R(2) =0.882). We tested a subset of compounds with the best MRI properties for toxicity and for activity as uncouplers, then obtained mice kidney CEST MRI images for three of the most promising leads finding 16 (2,4-dihydroxybenzoic acid) to be one of the most promising CEST MRI contrast agents to date. Overall, the results are of interest since they show that (1) H NMR shifts for CEST agents-charged species-can be well predicted, and that several leads have low toxicity and yield good in vivo MR images.

  9. Secukinumab: a promising therapeutic option in spondyloarthritis.

    PubMed

    Maldonado-Ficco, Hernan; Perez-Alamino, Rodolfo; Maldonado-Cocco, José A

    2016-09-01

    Psoriatic arthritis (PsA) is the second most common chronic inflammatory joint disease. Ankylosing spondylitis (AS) is another less common but equally chronic and disabling spondyloarthritis (SpA). Therapeutic agents for the treatment of these diseases have been somewhat lacking as compared with those available for rheumatoid arthritis, which represents a significant challenge for both the treating physician and the pharmaceutical industry. A promising development for our understanding of the physiopathology of PsA and AS involves new targets to interrupt IL-17 and IL-12/IL-23 pathways. Up to 30-40 % of SpA patients have inadequate or poor response, or are intolerant to anti-TNF therapies. Therefore, there has been a clear unmet medical need in an important group of these patients. As a result, new therapeutic targets have emerged for the treatment of both axial and peripheral SpA. Interleukin 17 (IL-17) is a pro-inflammatory cytokine that is increased in psoriatic lesions as well as in the synovial fluid of patients with PsA and in sites of enthesitis in SpA. IL-23 has been shown to play an important role in the polarization of CD4+ T-cells to become IL-17 producers. Based on these evidences, blockade of the cytokine IL-17 or its receptors was considered to have therapeutic implications for the treatment of psoriasis, as well as PsA and AS.This article presents a thorough review of an IL-17 A blocking agent, its mechanism of action, its clinical efficacy and its therapeutic safety. PMID:27437696

  10. Cancer and Inflammation: Promise for Biological Therapy

    PubMed Central

    Demaria, Sandra; Pikarsky, Eli; Karin, Michael; Coussens, Lisa M.; Chen, Yen-Ching; El-Omar, Emad M.; Trinchieri, Giorgio; Dubinett, Steven M.; Mao, Jenny T.; Szabo, Eva; Krieg, Arthur; Weiner, George J.; Fox, Bernard A.; Coukos, George; Wang, Ena; Abraham, Robert T.; Carbone, Michele; Lotze, Michael T.

    2010-01-01

    Cancers often arise as the end stage of inflammation in adults, but not in children. As such there is a complex interplay between host immune cells during neoplastic development, with both an ability to promote cancer as well as limit or eliminate it, most often complicit with the host. In humans, defining inflammation and the presence of inflammatory cells within or surrounding the tumor is a critical aspect of modern pathology. Groups defining staging for neoplasms are strongly encouraged to assess and incorporate measures of the presence of apoptosis, autophagy, and necrosis as well as the nature and quality of the immune infiltrate. Both environmental as well as genetic factors enhance the risk of cigarette smoking, H. pylori, hepatitis B/C, human papilloma virus, solar irradiation, asbestos, pancreatitis, or other causes of chronic inflammation. Identifying suitable genetic polymorphisms in cytokines, cytokine receptors, and Toll-like receptors among other immune response genes is also seen as high value as genomic sequencing becomes less expensive. Animal models which incorporate and assess not only the genetic anlagen but also the inflammatory cells and the presence of microbial pathogen [PAMPs] and damage associated molecular pattern molecules [DAMPs] are necessary. Identifying micro-RNAs involved in regulating the response to damage or injury are seen as highly promising. Although no therapeutic strategies to prevent or treat cancers based on insights into inflammatory pathways are currently approved for the common epithelial malignancies, there remains substantial interest in agents targeting COX2 or PPARγ, ethyl pyruvate, as well as steroids and several novel agents on the horizon. PMID:20386472

  11. Sunscreening Agents

    PubMed Central

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  12. International Collaboration: Promises and Challenges

    PubMed Central

    Widmer, R. Jay; Widmer, Jocelyn M.; Lerman, Amir

    2015-01-01

    We currently face a myriad of grand global challenges in fields such as poverty, the environment, education, science, and medicine. However, our current means of dealing with such challenges has fallen short, and ingenious solutions are required to overcome the inherent resistance to progress toward ameliorating such difficulties. Here, we highlight the promises and challenges of international collaboration in achieving success toward these trials. We note prior successes in fields such as education, medicine, science, and environmental issues made to date, yet at the same time we do note deficiencies and shortcomings in these efforts. Hence, the notion of international collaboration should be strengthened and encouraged by governments, non-profit organizations, and others moving forward using creative means to bring talented teams together to tackle these challenges across the globe. PMID:25973264

  13. Mangiferin: a promising anticancer bioactive.

    PubMed

    Khurana, Rajneet K; Kaur, Ranjot; Lohan, Shikha; Singh, Kamalinder K; Singh, Bhupinder

    2016-05-01

    Of late, several biologically active antioxidants from natural products have been investigated by the researchers in order to combat the root cause of carcinogenesis, in other words, oxidative stress. Mangiferin, a therapeutically active C-glucosylated xanthone, is extracted from pulp, peel, seed, bark and leaf of Mangifera indica. These polyphenols of mangiferin exhibit antioxidant properties and tend to decrease the oxygen-free radicals, thereby reducing the DNA damage. Indeed, its capability to modulate several key inflammatory pathways undoubtedly helps in stalling the progression of carcinogenesis. The current review article emphasizes an updated account on the patents published on the chemopreventive action of mangiferin, apoptosis induction made on various cancer cells, along with proposed antioxidative activities and patent mapping of other important therapeutic properties. Considering it as promising polyphenol, this paper would also summarize the diverse molecular targets of mangiferin. PMID:27088726

  14. Cultural Neuroscience: Progress and Promise

    PubMed Central

    Chiao, Joan Y.; Cheon, Bobby K.; Pornpattanangkul, Narun; Mrazek, Alissa J.; Blizinsky, Katherine D.

    2013-01-01

    The nature and origin of human diversity has been a source of intellectual curiosity since the beginning of human history. Contemporary advances in cultural and biological sciences provide unique opportunities for the emerging field of cultural neuroscience. Research in cultural neuroscience examines how cultural and genetic diversity shape the human mind, brain and behavior across multiple time scales: situation, ontogeny and phylogeny. Recent progress in cultural neuroscience provides novel theoretical frameworks for understanding the complex interaction of environmental, cultural and genetic factors in the production of adaptive human behavior. Here, we provide a brief history of cultural neuroscience, theoretical and methodological advances, as well as empirical evidence of the promise of and progress in the field. Implications of this research for population health disparities and public policy are discussed. PMID:23914126

  15. Mathematical Profiles and Problem Solving Abilities of Mathematically Promising Students

    ERIC Educational Resources Information Center

    Budak, Ibrahim

    2012-01-01

    Mathematically promising students are defined as those who have the potential to become the leaders and problem solvers of the future. The purpose of this research is to reveal what problem solving abilities mathematically promising students show in solving non-routine problems and type of profiles they present in the classroom and during problem…

  16. Television Quiz Show Simulation

    ERIC Educational Resources Information Center

    Hill, Jonnie Lynn

    2007-01-01

    This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.

  17. Ferrimagnetic susceptibility contrast agents.

    PubMed

    Bach-Gansmo, T

    1993-01-01

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

  18. Antiparasitic agents.

    PubMed

    Rosenblatt, J E

    1992-03-01

    In recent years, introduction of new and more effective agents has improved the overall therapy for parasitic infections. This field, however, is still plagued by numerous problems, including the development of resistance to antimicrobial agents (especially with malaria), unavailability of agents in the United States or lack of approval by the Food and Drug Administration, and major toxicities or lack of experience in pregnant women and children, which limits use in these groups of patients. Widespread resistance of Plasmodium falciparum to chloroquine and other agents has complicated the treatment and prophylaxis of this type of malaria. A combination of quinine and Fansidar is usually effective oral therapy for falciparum malaria; quinidine may be administered if intravenous therapy is needed. Mefloquine, which is currently recommended for prophylaxis against chloroquine-resistant P. falciparum, is also effective for single-dose oral treatment, although this regimen has not yet been approved by the Food and Drug Administration. Metronidazole has been widely used for treatment of gastroenteritis due to Entamoeba histolytica and Giardia lamblia (not approved by the Food and Drug Administration for the latter) and is considered safe and effective. A new macrolide, azithromycin, has been reported to be effective for cryptosporidiosis in experimental animals; currently, no effective therapy is available for human infections. Combinations of sulfonamides with other antifolates, trimethoprim or pyrimethamine, are recommended therapy for Pneumocystis carinii pneumonia or toxoplasmosis, respectively. Therapies for the various types of leishmaniasis and trypanosomiasis are complex, often toxic, and often of limited efficacy. The benzimidazoles are effective for roundworm infections, although thiabendazole has severe toxic effects. The recent introduction of ivermectin has revolutionized the treatment and control of onchocerciasis. Another relatively new agent, praziquantel

  19. Urinary PGE-M: a promising cancer biomarker.

    PubMed

    Wang, Dingzhi; DuBois, Raymond N

    2013-06-01

    Cancer prevention, early diagnosis, and targeted therapies are the keys to success in better cancer control and treatment. A big challenge remains to identify biomarkers for predicting who may have higher cancer risk and are able to respond to certain chemopreventive agents as well as for assessing a patient's response during treatment. Although a large body of evidence indicates that chronic inflammation is a risk factor for cancer, it is unclear whether inflammatory biomarkers can be used to predict cancer risk, progression, and death. Considering the importance of the proinflammatory COX-2-derived prostaglandin E2 (PGE2) in inflammation and cancer, Morris and colleagues found that urinary PGE-M is positively associated with obesity, smoking, and lung metastases in patients with breast cancer (4). Along the same lines, Kim and colleagues showed a potential association between urinary PGE-M and breast cancer risk in postmenopausal women (beginning on page 511). In agreement with previous reports, their findings indicate that urinary PGE-M may serve as a promising biomarker for prognosticating cancer risk and disease progression. PMID:23636051

  20. Antidiabetic Agents.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  1. Delivery of antifibroblast agents as adjuncts to filtration surgery. Part I--Periocular clearance of cobalt-57 bleomycin in experimental drug delivery: pilot study in the rabbit

    SciTech Connect

    Kay, J.S.; Litin, B.S.; Woolfenden, J.M.; Chvapil, M.; Herschler, J.

    1986-10-01

    Antitumor and antifibroblast agents show promise as adjuncts after glaucoma filtration surgery in reducing postoperative scarring and failure. We used nuclear imaging in rabbits to investigate periocular clearance of one such agent (/sup 57/Co-bleomycin). Sub-Tenon injection was compared to other delivery techniques. Our results showed that a collagen sponge and a silastic disc implant with a microhole prolonged drug delivery when compared to sub-Tenon injection alone or injection with a viscosity enhancing agent (0.5% sodium hyaluronate). We theorize that if an antifibroblast agent can be delivered in small and sustained amounts after filtration surgery, this may prolong bleb longevity and avoid unnecessary drug toxicity.

  2. Pea Plants Show Risk Sensitivity.

    PubMed

    Dener, Efrat; Kacelnik, Alex; Shemesh, Hagai

    2016-07-11

    Sensitivity to variability in resources has been documented in humans, primates, birds, and social insects, but the fit between empirical results and the predictions of risk sensitivity theory (RST), which aims to explain this sensitivity in adaptive terms, is weak [1]. RST predicts that agents should switch between risk proneness and risk aversion depending on state and circumstances, especially according to the richness of the least variable option [2]. Unrealistic assumptions about agents' information processing mechanisms and poor knowledge of the extent to which variability imposes specific selection in nature are strong candidates to explain the gap between theory and data. RST's rationale also applies to plants, where it has not hitherto been tested. Given the differences between animals' and plants' information processing mechanisms, such tests should help unravel the conflicts between theory and data. Measuring root growth allocation by split-root pea plants, we show that they favor variability when mean nutrient levels are low and the opposite when they are high, supporting the most widespread RST prediction. However, the combination of non-linear effects of nitrogen availability at local and systemic levels may explain some of these effects as a consequence of mechanisms not necessarily evolved to cope with variance [3, 4]. This resembles animal examples in which properties of perception and learning cause risk sensitivity even though they are not risk adaptations [5]. PMID:27374342

  3. Importance sampling : promises and limitations.

    SciTech Connect

    West, Nicholas J.; Swiler, Laura Painton

    2010-04-01

    Importance sampling is an unbiased sampling method used to sample random variables from different densities than originally defined. These importance sampling densities are constructed to pick 'important' values of input random variables to improve the estimation of a statistical response of interest, such as a mean or probability of failure. Conceptually, importance sampling is very attractive: for example one wants to generate more samples in a failure region when estimating failure probabilities. In practice, however, importance sampling can be challenging to implement efficiently, especially in a general framework that will allow solutions for many classes of problems. We are interested in the promises and limitations of importance sampling as applied to computationally expensive finite element simulations which are treated as 'black-box' codes. In this paper, we present a customized importance sampler that is meant to be used after an initial set of Latin Hypercube samples has been taken, to help refine a failure probability estimate. The importance sampling densities are constructed based on kernel density estimators. We examine importance sampling with respect to two main questions: is importance sampling efficient and accurate for situations where we can only afford small numbers of samples? And does importance sampling require the use of surrogate methods to generate a sufficient number of samples so that the importance sampling process does increase the accuracy of the failure probability estimate? We present various case studies to address these questions.

  4. A Holographic Road Show.

    ERIC Educational Resources Information Center

    Kirkpatrick, Larry D.; Rugheimer, Mac

    1979-01-01

    Describes the viewing sessions and the holograms of a holographic road show. The traveling exhibits, believed to stimulate interest in physics, include a wide variety of holograms and demonstrate several physical principles. (GA)

  5. The Ozone Show.

    ERIC Educational Resources Information Center

    Mathieu, Aaron

    2000-01-01

    Uses a talk show activity for a final assessment tool for students to debate about the ozone hole. Students are assessed on five areas: (1) cooperative learning; (2) the written component; (3) content; (4) self-evaluation; and (5) peer evaluation. (SAH)

  6. Show What You Know

    ERIC Educational Resources Information Center

    Eccleston, Jeff

    2007-01-01

    Big things come in small packages. This saying came to the mind of the author after he created a simple math review activity for his fourth grade students. Though simple, it has proven to be extremely advantageous in reinforcing math concepts. He uses this activity, which he calls "Show What You Know," often. This activity provides the perfect…

  7. Showing What They Know

    ERIC Educational Resources Information Center

    Cech, Scott J.

    2008-01-01

    Having students show their skills in three dimensions, known as performance-based assessment, dates back at least to Socrates. Individual schools such as Barrington High School--located just outside of Providence--have been requiring students to actively demonstrate their knowledge for years. The Rhode Island's high school graduating class became…

  8. Stage a Water Show

    ERIC Educational Resources Information Center

    Frasier, Debra

    2008-01-01

    In the author's book titled "The Incredible Water Show," the characters from "Miss Alaineus: A Vocabulary Disaster" used an ocean of information to stage an inventive performance about the water cycle. In this article, the author relates how she turned the story into hands-on science teaching for real-life fifth-grade students. The author also…

  9. What Do Maps Show?

    ERIC Educational Resources Information Center

    Geological Survey (Dept. of Interior), Reston, VA.

    This curriculum packet, appropriate for grades 4-8, features a teaching poster which shows different types of maps (different views of Salt Lake City, Utah), as well as three reproducible maps and reproducible activity sheets which complement the maps. The poster provides teacher background, including step-by-step lesson plans for four geography…

  10. Obesity in show cats.

    PubMed

    Corbee, R J

    2014-12-01

    Obesity is an important disease with a high prevalence in cats. Because obesity is related to several other diseases, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain cat breeds has been suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, 268 cats of 22 different breeds investigated by determining their body condition score (BCS) on a nine-point scale by inspection and palpation, at two different cat shows. Overall, 45.5% of the show cats had a BCS > 5, and 4.5% of the show cats had a BCS > 7. There were significant differences between breeds, which could be related to the breed standards. Most overweight and obese cats were in the neutered group. It warrants firm discussions with breeders and cat show judges to come to different interpretations of the standards in order to prevent overweight conditions in certain breeds from being the standard of beauty. Neutering predisposes for obesity and requires early nutritional intervention to prevent obese conditions. PMID:24612018

  11. Show Me the Way

    ERIC Educational Resources Information Center

    Dicks, Matthew J.

    2005-01-01

    Because today's students have grown up steeped in video games and the Internet, most of them expect feedback, and usually gratification, very soon after they expend effort on a task. Teachers can get quick feedback to students by showing them videotapes of their learning performances. The author, a 3rd grade teacher describes how the seemingly…

  12. The Art Show

    ERIC Educational Resources Information Center

    Scolarici, Alicia

    2004-01-01

    This article describes what once was thought to be impossible--a formal art show extravaganza at an elementary school with 1,000 students, a Department of Defense Dependent School (DODDS) located overseas, on RAF Lakenheath, England. The dream of this this event involved the transformation of the school cafeteria into an elegant art show…

  13. Honored Teacher Shows Commitment.

    ERIC Educational Resources Information Center

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  14. A Promising Development: "Promise" Scholarships Targeting Individual Communities Reduce Barriers to College Access--and Completion

    ERIC Educational Resources Information Center

    Pierce, Dennis

    2015-01-01

    This article discusses Promise Scholarships in community colleges and sources of funding. The following community colleges and their scholarships are mentioned in this article: (1) Oregon Promise, Oregon; (2) Ventura College Promise, California; (3) Kalamazoo Promise, Michigan; (4) Pittsburgh Promise, Pennsylvania; (5) SEED Scholarship, Delaware;…

  15. Agent amplified communication

    SciTech Connect

    Kautz, H.; Selman, B.; Milewski, A.

    1996-12-31

    We propose an agent-based framework for assisting and simplifying person-to-person communication for information gathering tasks. As an example, we focus on locating experts for any specified topic. In our approach, the informal person-to-person networks that exist within an organization are used to {open_quotes}referral chain{close_quotes} requests for expertise. User-agents help automate this process. The agents generate referrals by analyzing records of e-mail communication patterns. Simulation results show that the higher responsiveness of an agent-based system can be effectively traded for the higher accuracy of a completely manual approach. Furthermore, preliminary experience with a group of users on a prototype system has shown that useful automatic referrals can be found in practice. Our experience with actual users has also shown that privacy concerns are central to the successful deployment of personal agents: an advanced agent-based system will therefore need to reason about issues involving trust and authority.

  16. Taking in a Show.

    PubMed

    Boden, Timothy W

    2016-01-01

    Many medical practices have cut back on education and staff development expenses, especially those costs associated with conventions and conferences. But there are hard-to-value returns on your investment in these live events--beyond the obvious benefits of acquired knowledge and skills. Major vendors still exhibit their services and wares at many events, and the exhibit hall is a treasure-house of information and resources for the savvy physician or administrator. Make and stick to a purposeful plan to exploit the trade show. You can compare products, gain new insights and ideas, and even negotiate better deals with representatives anxious to realize returns on their exhibition investments. PMID:27249887

  17. Taking in a Show.

    PubMed

    Boden, Timothy W

    2016-01-01

    Many medical practices have cut back on education and staff development expenses, especially those costs associated with conventions and conferences. But there are hard-to-value returns on your investment in these live events--beyond the obvious benefits of acquired knowledge and skills. Major vendors still exhibit their services and wares at many events, and the exhibit hall is a treasure-house of information and resources for the savvy physician or administrator. Make and stick to a purposeful plan to exploit the trade show. You can compare products, gain new insights and ideas, and even negotiate better deals with representatives anxious to realize returns on their exhibition investments.

  18. Obesity in show dogs.

    PubMed

    Corbee, R J

    2013-10-01

    Obesity is an important disease with a growing incidence. Because obesity is related to several other diseases, and decreases life span, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain breeds is often suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, we investigated 1379 dogs of 128 different breeds by determining their body condition score (BCS). Overall, 18.6% of the show dogs had a BCS >5, and 1.1% of the show dogs had a BCS>7. There were significant differences between breeds, which could be correlated to the breed standards. It warrants firm discussions with breeders and judges in order to come to different interpretations of the standards to prevent overweight conditions from being the standard of beauty. PMID:22882163

  19. Baltimore Community Schools: Promise & Progress

    ERIC Educational Resources Information Center

    Durham, Rachel E.; Connolly, Faith

    2016-01-01

    This report documents the interim progress of the Baltimore Community School (CommSch) strategy by examining outcomes for the 2014-15 school year. Results show that CommSch parents more often reported being connected with community resources by school staff compared to parents at other schools. They also were more likely to report that school…

  20. KGB agents

    NASA Astrophysics Data System (ADS)

    Gaina, Alex

    A short story is reported in which the activity of Communist Party of the USSR and secret KGB agents, which were payed by the State, in view of controlling of the conscience of population. The story reffers to the Physics Department of the Moscow University, Planing Institute of the Gosplan of Moldavian S.S.R. and Chishinau Technical University (actually: Technical University of Moldova), where the author has worked during Soviet times. Almost every 6-th citizen in the USSR was engaged in this activity, while actually the former communists rule in the Republic of Moldova.

  1. Not a "reality" show.

    PubMed

    Wrong, Terence; Baumgart, Erica

    2013-01-01

    The authors of the preceding articles raise legitimate questions about patient and staff rights and the unintended consequences of allowing ABC News to film inside teaching hospitals. We explain why we regard their fears as baseless and not supported by what we heard from individuals portrayed in the filming, our decade-long experience making medical documentaries, and the full un-aired context of the scenes shown in the broadcast. The authors don't and can't know what conversations we had, what documents we reviewed, and what protections we put in place in each televised scene. Finally, we hope to correct several misleading examples cited by the authors as well as their offhand mischaracterization of our program as a "reality" show. PMID:23631336

  2. Not a "reality" show.

    PubMed

    Wrong, Terence; Baumgart, Erica

    2013-01-01

    The authors of the preceding articles raise legitimate questions about patient and staff rights and the unintended consequences of allowing ABC News to film inside teaching hospitals. We explain why we regard their fears as baseless and not supported by what we heard from individuals portrayed in the filming, our decade-long experience making medical documentaries, and the full un-aired context of the scenes shown in the broadcast. The authors don't and can't know what conversations we had, what documents we reviewed, and what protections we put in place in each televised scene. Finally, we hope to correct several misleading examples cited by the authors as well as their offhand mischaracterization of our program as a "reality" show.

  3. Multiscale agent-based consumer market modeling.

    SciTech Connect

    North, M. J.; Macal, C. M.; St. Aubin, J.; Thimmapuram, P.; Bragen, M.; Hahn, J.; Karr, J.; Brigham, N.; Lacy, M. E.; Hampton, D.; Decision and Information Sciences; Procter & Gamble Co.

    2010-05-01

    Consumer markets have been studied in great depth, and many techniques have been used to represent them. These have included regression-based models, logit models, and theoretical market-level models, such as the NBD-Dirichlet approach. Although many important contributions and insights have resulted from studies that relied on these models, there is still a need for a model that could more holistically represent the interdependencies of the decisions made by consumers, retailers, and manufacturers. When the need is for a model that could be used repeatedly over time to support decisions in an industrial setting, it is particularly critical. Although some existing methods can, in principle, represent such complex interdependencies, their capabilities might be outstripped if they had to be used for industrial applications, because of the details this type of modeling requires. However, a complementary method - agent-based modeling - shows promise for addressing these issues. Agent-based models use business-driven rules for individuals (e.g., individual consumer rules for buying items, individual retailer rules for stocking items, or individual firm rules for advertizing items) to determine holistic, system-level outcomes (e.g., to determine if brand X's market share is increasing). We applied agent-based modeling to develop a multi-scale consumer market model. We then conducted calibration, verification, and validation tests of this model. The model was successfully applied by Procter & Gamble to several challenging business problems. In these situations, it directly influenced managerial decision making and produced substantial cost savings.

  4. Public medical shows.

    PubMed

    Walusinski, Olivier

    2014-01-01

    In the second half of the 19th century, Jean-Martin Charcot (1825-1893) became famous for the quality of his teaching and his innovative neurological discoveries, bringing many French and foreign students to Paris. A hunger for recognition, together with progressive and anticlerical ideals, led Charcot to invite writers, journalists, and politicians to his lessons, during which he presented the results of his work on hysteria. These events became public performances, for which physicians and patients were transformed into actors. Major newspapers ran accounts of these consultations, more like theatrical shows in some respects. The resultant enthusiasm prompted other physicians in Paris and throughout France to try and imitate them. We will compare the form and substance of Charcot's lessons with those given by Jules-Bernard Luys (1828-1897), Victor Dumontpallier (1826-1899), Ambroise-Auguste Liébault (1823-1904), Hippolyte Bernheim (1840-1919), Joseph Grasset (1849-1918), and Albert Pitres (1848-1928). We will also note their impact on contemporary cinema and theatre. PMID:25273491

  5. Neuraminidase inhibitor R-125489 - A promising drug for treating influenza virus: Steered molecular dynamics approach

    SciTech Connect

    Mai, Binh Khanh; Li, Mai Suan

    2011-07-08

    Highlights: {yields} We study binding affinity of R-125489 and its prodrug CS-8958 to neuraminidase of pathogenic influenza viruses by molecular dynamics simulations. {yields} It is shown that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. {yields} We predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus. {yields} The high correlation between theoretical and experimental data implies that SMD is a very promising tool for drug design. -- Abstract: Two neuraminidase inhibitors, oseltamivir and zanamivir, are important drug treatments for influenza. Oseltamivir-resistant mutants of the influenza virus A/H1N1 and A/H5N1 have emerged, necessitating the development of new long-acting antiviral agents. One such agent is a new neuraminidase inhibitor R-125489 and its prodrug CS-8958. An atomic level understanding of the nature of this antiviral agents binding is still missing. We address this gap in our knowledge by applying steered molecular dynamics (SMD) simulations to different subtypes of seasonal and highly pathogenic influenza viruses. We show that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. Based on results obtained by SMD and the molecular mechanics-Poisson-Boltzmann surface area method, we predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus as its binding affinity does not vary much across these systems. The high correlation level between theoretically determined rupture forces and experimental data on binding energies for the large number of systems studied here implies that SMD is a promising tool for drug design.

  6. The Great Cometary Show

    NASA Astrophysics Data System (ADS)

    2007-01-01

    its high spatial and spectral resolution, it was possible to zoom into the very heart of this very massive star. In this innermost region, the observations are dominated by the extremely dense stellar wind that totally obscures the underlying central star. The AMBER observations show that this dense stellar wind is not spherically symmetric, but exhibits a clearly elongated structure. Overall, the AMBER observations confirm that the extremely high mass loss of Eta Carinae's massive central star is non-spherical and much stronger along the poles than in the equatorial plane. This is in agreement with theoretical models that predict such an enhanced polar mass-loss in the case of rapidly rotating stars. ESO PR Photo 06c/07 ESO PR Photo 06c/07 RS Ophiuchi in Outburst Several papers from this special feature focus on the later stages in a star's life. One looks at the binary system Gamma 2 Velorum, which contains the closest example of a star known as a Wolf-Rayet. A single AMBER observation allowed the astronomers to separate the spectra of the two components, offering new insights in the modeling of Wolf-Rayet stars, but made it also possible to measure the separation between the two stars. This led to a new determination of the distance of the system, showing that previous estimates were incorrect. The observations also revealed information on the region where the winds from the two stars collide. The famous binary system RS Ophiuchi, an example of a recurrent nova, was observed just 5 days after it was discovered to be in outburst on 12 February 2006, an event that has been expected for 21 years. AMBER was able to detect the extension of the expanding nova emission. These observations show a complex geometry and kinematics, far from the simple interpretation of a spherical fireball in extension. AMBER has detected a high velocity jet probably perpendicular to the orbital plane of the binary system, and allowed a precise and careful study of the wind and the shockwave

  7. Court rules insurer must honor its promise.

    PubMed

    1998-10-01

    Monumental Life Insurance Co. has to pay more than $230,000 to a beneficiary whose partner died of AIDS, shortly after paying the monthly premium for a life insurance policy. Unaware of the health status of the policy holder, a representative from the insurance company granted coverage and gave the policy holder a written statement that showed the amount of coverage of the policy. After the death of the partner, the insurance company told the beneficiary that the amount of coverage promised was a mistake. The beneficiary sued, and it was ruled that the company's letter, and the payment of the monthly premium, constituted a contract that the insurance company was obligated to uphold.

  8. Stretched View Showing 'Victoria'

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Stretched View Showing 'Victoria'

    This pair of images from the panoramic camera on NASA's Mars Exploration Rover Opportunity served as initial confirmation that the two-year-old rover is within sight of 'Victoria Crater,' which it has been approaching for more than a year. Engineers on the rover team were unsure whether Opportunity would make it as far as Victoria, but scientists hoped for the chance to study such a large crater with their roving geologist. Victoria Crater is 800 meters (nearly half a mile) in diameter, about six times wider than 'Endurance Crater,' where Opportunity spent several months in 2004 examining rock layers affected by ancient water.

    When scientists using orbital data calculated that they should be able to detect Victoria's rim in rover images, they scrutinized frames taken in the direction of the crater by the panoramic camera. To positively characterize the subtle horizon profile of the crater and some of the features leading up to it, researchers created a vertically-stretched image (top) from a mosaic of regular frames from the panoramic camera (bottom), taken on Opportunity's 804th Martian day (April 29, 2006).

    The stretched image makes mild nearby dunes look like more threatening peaks, but that is only a result of the exaggerated vertical dimension. This vertical stretch technique was first applied to Viking Lander 2 panoramas by Philip Stooke, of the University of Western Ontario, Canada, to help locate the lander with respect to orbiter images. Vertically stretching the image allows features to be more readily identified by the Mars Exploration Rover science team.

    The bright white dot near the horizon to the right of center (barely visible without labeling or zoom-in) is thought to be a light-toned outcrop on the far wall of the crater, suggesting that the rover can see over the low rim of Victoria. In figure 1, the northeast and southeast rims are labeled

  9. Morin: A Promising Natural Drug.

    PubMed

    Caselli, Anna; Cirri, Paolo; Santi, Alice; Paoli, Paolo

    2016-01-01

    Morin is a natural polyphenol, originally isolated from members of the Moraceae family that can be extracted from leaves, fruits, stems and branches of numerous plants. Several evidence have demonstrated that Morin could have a beneficial effect on several human diseases. In fact, Morin exerts antioxidant, antidiabetic, anti-inflammatory, antitumoral, antihypertensive, antibacterial, hypouricemic, and neuroprotective effects, by modulating the activity of many enzymes. In some cases, Morin shows a systemic protective action, reducing negative side effects of several drugs, without interfering with their functions. In addition, in vitro and in vivo studies demonstrated that Morin exhibits very low toxicity levels and its chronic administration is well tolerated. All these findings suggest that Morin could be used, either alone or in combination with other drugs, to prevent many human pathologies.

  10. Filling agents.

    PubMed

    Glavas, Ioannis P

    2005-06-01

    Injectable fillers have become an important component of minimally invasive facial rejuvenation modalities. Their ease of use, effectiveness, low morbidity, and fast results with minimal downtime are factors that have made them popular among patients. Soft tissue augmentation has evolved to a unique combination of medicine and art. A wide selection of available agents and new products, each one with unique properties, may be used alone or in combination. The physician acquires the tools to rebalance facial characteristics not only by filling wrinkles but also by having the ability to shape the face and restore bony contours and lines. Careful selection of candidates, realistic expectations, and an understanding of the limitations of fillers are crucial for a successful result.

  11. A New F-18 Labeled PET Agent For Imaging Alzheimer's Plaques

    SciTech Connect

    Kulkarni, Padmakar V.; Hao Guiyang; Arora, Veera; Long, Michael; Slavine, Nikolai; Chiguru, Srinivas; Qu Baoxi; Sun Xiankai; Bennett, Michael; Antich, Peter P.; Bonte, Frederick J.; Vasdev, Neil

    2011-06-01

    Amyloid plaques and neurofibrillary tangles are hallmarks of Alzheimer's disease (AD). Advances in development of imaging agents have focused on targeting amyloid plaques. Notable success has been the development of C-11 labeled PIB (Pittsburgh Compound) and a number of studies have demonstrated the utility of this agent. However, the short half life of C-11 (t1/2: 20 min), is a limitation, thus has prompted the development of F-18 labeled agents. Most of these agents are derivatives of amyloid binding dyes; Congo red and Thioflavin. Some of these agents are in clinical trials with encouraging results. We have been exploring new class of agents based on 8-hydroxy quinoline, a weak metal chelator, targeting elevated levels of metals in plaques. Iodine-123 labeled clioquinol showed affinity for amyloid plaques however, it had limited brain uptake and was not successful in imaging in intact animals and humans. We have been successful in synthesizing F-18 labeled 8-hydroxy quinoline. Small animal PET/CT imaging studies with this agent showed high (7-10% ID/g), rapid brain uptake and fast washout of the agent from normal mice brains and delayed washout from transgenic Alzheimer's mice. These promising results encouraged us in further evaluation of this class of compounds for imaging AD plaques.

  12. Chondroitinase: A promising therapeutic enzyme.

    PubMed

    Kasinathan, Narayanan; Volety, Subrahmanyam M; Josyula, Venkata Rao

    2016-05-01

    Even after 20 years of granting orphan status for chondroitinase by US FDA, there is no visible outcome in terms of clinical use. The reasons are many. One of them could be lack of awareness regarding the biological application of the enzyme. The biological activity of chondroitinase is due to its ability to act on chondroitin sulfate proteoglycans (CSPGs). CSPGs are needed for normal functioning of the body. An increase or decrease in the level of CSPGs results in various pathological conditions. Chondroitinase is useful in conditions where there is an increase in the level of CSPGs, namely spinal cord injury, vitreous attachment and cancer. Over the last decade, various animal studies showed that chondroitinase could be a good drug candidate. Research focusing on developing a suitable carrier system for delivering chondroitinase needs to be carried out so that pharmacological activity observed in vitro and preclinical studies could be translated to clinical use. Further studies on distribution of chondroitinase as well need to be focused so that chondroitinase with desired attributes could be discovered. The present review article discusses about various biological applications of chondroitinase, drug delivery systems to deliver the enzyme and distribution of chondroitinase among microbes.

  13. Space Shuttle: The Renewed Promise

    NASA Technical Reports Server (NTRS)

    McAleer, Neil

    1989-01-01

    NASA celebrated its 30th anniversary in 1988, two days after the Space Shuttle soared into space once more. When Congress approved the creation of the National Aeronautics and Space Administration in 1958, the United States had successfully launched only four small satellites and no American astronaut had yet flown in space. In the three decades since, four generations of manned spacecraft have been built and flown, twelve men have walked on the Moon, more than 100 Americans have flown and worked in space, and communications satellites and other Space-Age technologies have transformed life on planet Earth. When NASA's Golden Anniversary is celebrated in 2008, it is likely that men and women will be permanently living and working in space. There may be a base on the Moon, and a manned mission to Mars may only be years away. If a brief history of the first half-century of the Space Age is written for that event, it will show clearly how the exploration of space has altered the course of human history and allowed us to take a better hold of our destiny on and off planet Earth.

  14. The Promise for Starry Eyes

    NASA Astrophysics Data System (ADS)

    Pazmino, John

    2001-06-01

    In this slidetalk, supplemented by a poster exhibit, a status report on New York City's ongoing eradication of luminous graffiti as of the end of the 20th century was laid out. The focus was on Manhattan, the core of the Big Apple. Streetlamps are under global replacement in many parts of Manhattan, including Midtown, Greenwich Village, City Hall, and Lower Manhattan, with a variety of new lamps to give star-friendly illumination on the street. By the turn of the new millennium, the City achieved essentially complete evisceration of light pollution from store and facade lighting. This is a direct spinoff of the theme that stores on Manhattan must redo their frontages every three to five years to conform to the modern codes for illumination. Area and grounds lighting of immense corporate and commercial facilities stresses shielded, modest, occulted lamps. These include footlamps in parapets and sidewalls, lamppoles with large hoods, sconce lamps, ballards with concealed lamps. The World Trade Center, by a combination of these features, emits less light into the sky than a typcial rural truck stop, despite it being quite the equal in urban activity as all of downtown Boston. Astronomers in New York can monitor their progress toward a star-friendly cityscape from the tops of the towers. From here, they see New York from the eye of a star! Photographs from the Empire State Buidling showed that on the whole Manhattan--a conurabtion equal to the region around San Diego, Miami, or Boston, already sends fewer excess skyward photons than it suburbs across the rivers. With the accomplishments so far and with continuing work in progress, our profession set itself the goal that before this decade, the first in the new millennium, is over we will see the Milky Way from Manhattan--and see it with the bare eye.

  15. 76 FR 55889 - Reopening Notice: Promise Neighborhoods Program-Implementation Grant Competition; Promise...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... review 84.215N: Promise Neighborhoods Program-- 7/6/2011 76 FR 39615 9/06/2011 9/13/2011 11/03/2011 11/10/2011 Implementation. 84.215P: Promise Neighborhoods Program-- 7/06/2011 76 FR 39630 9/06/2011 9/13/2011... Reopening Notice: Promise Neighborhoods Program--Implementation Grant Competition; Promise...

  16. Health care agents

    MedlinePlus

    Durable power of attorney for health care; Health care proxy; End-of-life - health care agent; Life support treatment - ... Respirator - health care agent; Ventilator - health care agent; Power of attorney - health care agent; POA - health care ...

  17. Relational agents in clinical psychiatry.

    PubMed

    Bickmore, Timothy; Gruber, Amanda

    2010-01-01

    Relational agents are computational artifacts, such as animated, screen-based characters or social robots, that are designed to establish a sense of rapport, trust, and even therapeutic alliance with patients, using ideal therapeutic relationships between human counselors and patients as role models. We describe the development and evaluation of several such agents designed for health counseling and behavioral-change interventions, in which a therapeutic alliance is established with patients in order to enhance the efficacy of the intervention. We also discuss the promise of using such agents as adjuncts to clinical psychiatry, a range of possible applications, and some of the challenges and ethical issues in developing and fielding them in psychiatric interventions.

  18. Collaborating Fuzzy Reinforcement Learning Agents

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.

    1997-01-01

    Earlier, we introduced GARIC-Q, a new method for doing incremental Dynamic Programming using a society of intelligent agents which are controlled at the top level by Fuzzy Relearning and at the local level, each agent learns and operates based on ANTARCTIC, a technique for fuzzy reinforcement learning. In this paper, we show that it is possible for these agents to compete in order to affect the selected control policy but at the same time, they can collaborate while investigating the state space. In this model, the evaluator or the critic learns by observing all the agents behaviors but the control policy changes only based on the behavior of the winning agent also known as the super agent.

  19. 32 CFR 552.78 - “Show cause” hearing.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....78 “Show cause” hearing. Before suspending the solicitation privilege, the company and the agent will have a chance to show cause why the action should not be taken. “Show cause” is an opportunity for...

  20. 32 CFR 552.78 - “Show cause” hearing.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....78 “Show cause” hearing. Before suspending the solicitation privilege, the company and the agent will have a chance to show cause why the action should not be taken. “Show cause” is an opportunity for...

  1. 32 CFR 552.78 - “Show cause” hearing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....78 “Show cause” hearing. Before suspending the solicitation privilege, the company and the agent will have a chance to show cause why the action should not be taken. “Show cause” is an opportunity for...

  2. 32 CFR 552.78 - “Show cause” hearing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....78 “Show cause” hearing. Before suspending the solicitation privilege, the company and the agent will have a chance to show cause why the action should not be taken. “Show cause” is an opportunity for...

  3. 32 CFR 552.78 - “Show cause” hearing.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....78 “Show cause” hearing. Before suspending the solicitation privilege, the company and the agent will have a chance to show cause why the action should not be taken. “Show cause” is an opportunity for...

  4. Detecting agents.

    PubMed Central

    Johnson, Susan C

    2003-01-01

    This paper reviews a recent set of behavioural studies that examine the scope and nature of the representational system underlying theory-of-mind development. Studies with typically developing infants, adults and children with autism all converge on the claim that there is a specialized input system that uses not only morphological cues, but also behavioural cues to categorize novel objects as agents. Evidence is reviewed in which 12- to 15-month-old infants treat certain non-human objects as if they have perceptual/attentional abilities, communicative abilities and goal-directed behaviour. They will follow the attentional orientation of an amorphously shaped novel object if it interacts contingently with them or with another person. They also seem to use a novel object's environmentally directed behaviour to determine its perceptual/attentional orientation and object-oriented goals. Results from adults and children with autism are strikingly similar, despite adults' contradictory beliefs about the objects in question and the failure of children with autism to ultimately develop more advanced theory-of-mind reasoning. The implications for a general theory-of-mind development are discussed. PMID:12689380

  5. Isoform-specific inhibitors of ACATs: recent advances and promising developments.

    PubMed

    Ohshiro, Taichi; Tomoda, Hiroshi

    2011-12-01

    Acyl-CoA:cholesterol acyltransferase (ACAT) is a promising therapeutic target for cardiovascular diseases. Although a number of synthetic ACAT inhibitors have been developed, they have failed to show efficacy in clinical trials. Now, the presence of two ACAT isoforms with distinct functions, ACAT1 and ACAT2, has been discovered. Thus, the selectivity of ACAT inhibitors toward the two isoforms is important for their development as novel anti-atherosclerotic agents. The selectivity study indicated that fungal pyripyropene A (PPPA) is only an ACAT2-specific inhibitor. Furthermore, PPPA proved orally active in atherogenic mouse models, indicating it possessed cholesterol-lowering and atheroprotective activities. Certain PPPA derivatives, semi-synthetically prepared, possessed more potent and selective in vitro activity than PPPA against ACAT2. This review covers these studies and describes the future prospects of ACAT2-specific inhibitors. PMID:22098352

  6. The Promising Syllabus Enacted: One Teacher's Experience

    ERIC Educational Resources Information Center

    Hirsch, Christine Courtade

    2010-01-01

    The purpose of this report is to describe a rationale and strategies for use of the Promising Syllabus (in Bain, 2004, What the best college teachers do). This syllabus reflects the learner-centered paradigm where students take charge of their own learning. The syllabus creates a series of promises between teacher and student, focusing on a…

  7. Molten Wax As A Dust Control Agent

    SciTech Connect

    Carter, E.E.

    2008-07-01

    Molten wax shows considerable promise as a fixative and dust control agent in demolition of radioactively contaminated facilities. Sticky molten wax, modified with special surfactants and wetting agents, is capable of not only coating materials but also penetrating into friable or dusty materials and making them incapable of becoming airborne during demolition. Wax also shows significant promise for stabilization of waste residuals that may be contained in buildings undergoing demolition. Some of the building materials that have been tested to date include concrete, wood, sheet-rock, fiber insulation, lime, rock, and paper. Protective clothing, clay, sand, sulfur, and bentonite clay have been tested as surrogates for certain waste materials that may be encountered during building demolition. The paper describes several potential applications of molten wax for dust control in demolition of radioactive contaminated facilities. As a case-study, this paper describes a research test performed for a pipeline closure project being completed by the Idaho Cleanup Project at the Idaho National Laboratory. The project plans to excavate and remove a section of buried Duriron drain piping containing highly radioactive and friable and 'flighty' waste residuals. A full-scale pipeline mockup containing simulated waste was buried in sand to simulate the direct-buried subsurface condition of the subject piping. The pipeline was pre-heated by drawing hot air through the line with a HEPA vacuum blower unit. Molten wax was pumped into the line and allowed to cool. The line was then broken apart in various places to evaluate the permeation performance of the wax. The wax fully permeated all the surrogate materials rendering them non-friable with a consistency similar to modeling clay. Based on the performance during the mockup, it is anticipated that the wax will be highly effective in controlling the spread of radiological contamination during pipe demolition activities. A larger test

  8. Introduction to Agent Mining Interaction and Integration

    NASA Astrophysics Data System (ADS)

    Cao, Longbing

    In recent years, more and more researchers have been involved in research on both agent technology and data mining. A clear disciplinary effort has been activated toward removing the boundary between them, that is the interaction and integration between agent technology and data mining. We refer this to agent mining as a new area. The marriage of agents and data mining is driven by challenges faced by both communities, and the need of developing more advanced intelligence, information processing and systems. This chapter presents an overall picture of agent mining from the perspective of positioning it as an emerging area. We summarize the main driving forces, complementary essence, disciplinary framework, applications, case studies, and trends and directions, as well as brief observation on agent-driven data mining, data mining-driven agents, and mutual issues in agent mining. Arguably, we draw the following conclusions: (1) agent mining emerges as a new area in the scientific family, (2) both agent technology and data mining can greatly benefit from agent mining, (3) it is very promising to result in additional advancement in intelligent information processing and systems. However, as a new open area, there are many issues waiting for research and development from theoretical, technological and practical perspectives.

  9. Inhibition of Sulfide Mineral Oxidation by Surface Coating Agents: Batch

    NASA Astrophysics Data System (ADS)

    Choi, J.; Ji, M. K.; Yun, H. S.; Park, Y. T.; Gee, E. D.; Lee, W. R.; Jeon, B.-H.

    2012-04-01

    Mining activities and mineral industries have impacted on rapid oxidation of sulfide minerals such as pyrite (FeS2) which leads to Acid Mine Drainage (AMD) formation. Some of the abandoned mines discharge polluted water without proper environmental remediation treatments, largely because of financial constraints in treating AMD. Magnitude of the problem is considerable, especially in countries with a long history of mining. As metal sulfides become oxidized during mining activities, the aqueous environment becomes acid and rich in many metals, including iron, lead, mercury, arsenic and many others. The toxic heavy metals are responsible for the environmental deterioration of stream, groundwater and soils. Several strategies to remediate AMD contaminated sites have been proposed. Among the source inhibition and prevention technologies, microencapsulation (coating) has been considered as a promising technology. The encapsulation is based on inhibition of O2 diffusion by surface coating agent and is expected to control the oxidation of pyrite for a long time. Potential of several surface coating agents for preventing oxidation of metal sulfide minerals from both Young-Dong coal mine and Il-Gwang gold mine were examined by conducting batch experiments and field tests. Powdered pyrite as a standard sulfide mineral and rock samples from two mine outcrops were mixed with six coating agents (KH2PO4, MgO and KMnO4 as chemical agents, and apatite, cement and manganite as mineral agents) and incubated with oxidizing agents (H2O2 or NaClO). Batch experiments with Young-Dong coal mine samples showed least SO42- production in presence of KMnO4 (16% sulfate production compared to no surface coating agents) or cement (4%) within 8 days. In the case of Il-Gwang mine samples, least SO42- production was observed in presence of KH2PO4 (8%) or cement (2%) within 8 days. Field-scale pilot tests at Il-Gwang site also showed that addition of KH2PO4 decreased sulfate production from 200 to

  10. CHAMPION: Intelligent Hierarchical Reasoning Agents for Enhanced Decision Support

    SciTech Connect

    Hohimer, Ryan E.; Greitzer, Frank L.; Noonan, Christine F.; Strasburg, Jana D.

    2011-11-15

    We describe the design and development of an advanced reasoning framework employing semantic technologies, organized within a hierarchy of computational reasoning agents that interpret domain specific information. Designed based on an inspirational metaphor of the pattern recognition functions performed by the human neocortex, the CHAMPION reasoning framework represents a new computational modeling approach that derives invariant knowledge representations through memory-prediction belief propagation processes that are driven by formal ontological language specification and semantic technologies. The CHAMPION framework shows promise for enhancing complex decision making in diverse problem domains including cyber security, nonproliferation and energy consumption analysis.

  11. Amino acid–based surfactants: New antimicrobial agents.

    PubMed

    Pinazo, A; Manresa, M A; Marques, A M; Bustelo, M; Espuny, M J; Pérez, L

    2016-02-01

    The rapid increase of drug resistant bacteria makes necessary the development of new antimicrobial agents. Synthetic amino acid-based surfactants constitute a promising alternative to conventional antimicrobial compounds given that they can be prepared from renewable raw materials. In this review, we discuss the structural features that promote antimicrobial activity of amino acid-based surfactants. Monocatenary, dicatenary and gemini surfactants that contain different amino acids on the polar head and show activity against bacteria are revised. The synthesis and basic physico-chemical properties have also been included.

  12. [Efficacy of the Russian anthelmintic agent trichlorophen].

    PubMed

    Fedianina, L V; Gitsu, G A; Lebedeva, M N; Astaf'ev, B A

    2004-01-01

    Experiments have established the high efficacy of combinations of the micronized dosage form of trichlorophen, with albendazole or medamine in treating trichocephaliasis (its causative agent being Trichocephalus muris) in DBA/2st mice and that of trichlorophen in combination with azinox or fenasal in outbred albino mice with hymenolepiasis (its causative agent being Hymenolepis nana). These combinations are promising in treating patients with cestodosis and nemadosis, respectively. PMID:15042750

  13. Magnetic nanobeads as potential contrast agents for magnetic resonance imaging.

    PubMed

    Pablico-Lansigan, Michele H; Hickling, William J; Japp, Emily A; Rodriguez, Olga C; Ghosh, Anup; Albanese, Chris; Nishida, Maki; Van Keuren, Edward; Fricke, Stanley; Dollahon, Norman; Stoll, Sarah L

    2013-10-22

    Metal-oxo clusters have been used as building blocks to form hybrid nanomaterials and evaluated as potential MRI contrast agents. We have synthesized a biocompatible copolymer based on a water stable, nontoxic, mixed-metal-oxo cluster, Mn8Fe4O12(L)16(H2O)4, where L is acetate or vinyl benzoic acid, and styrene. The cluster alone was screened by NMR for relaxivity and was found to be a promising T2 contrast agent, with r1 = 2.3 mM(-1) s(-1) and r2 = 29.5 mM(-1) s(-1). Initial cell studies on two human prostate cancer cell lines, DU-145 and LNCap, reveal that the cluster has low cytotoxicity and may be potentially used in vivo. The metal-oxo cluster Mn8Fe4(VBA)16 (VBA = vinyl benzoic acid) can be copolymerized with styrene under miniemulsion conditions. Miniemulsion allows for the formation of nanometer-sized paramagnetic beads (~80 nm diameter), which were also evaluated as a contrast agent for MRI. These highly monodispersed, hybrid nanoparticles have enhanced properties, with the option for surface functionalization, making them a promising tool for biomedicine. Interestingly, both relaxivity measurements and MRI studies show that embedding the Mn8Fe4 core within a polymer matrix decreases r2 effects with little effect on r1, resulting in a positive T1 contrast enhancement.

  14. Investigational Antimicrobial Agents of 2013

    PubMed Central

    Pucci, Michael J.

    2013-01-01

    SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

  15. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    2000-02-08

    Bicyclo[2.2.2]octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo[2.2.1]heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  16. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, M.P.; Mease, R.C.; Srivastava, S.C.

    1998-07-21

    Bicyclo[2.2.2] octane-2,3 diamine-N,N,N`,N`-tetraacetic acids (BODTA) and bicyclo[2.2.1] heptane-2,3 diamine-N,N,N`,N`-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  17. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    1998-07-21

    Bicyclo›2.2.2! octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo›2.2.1! heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  18. Development of Class IIa Bacteriocins as Therapeutic Agents

    PubMed Central

    Lohans, Christopher T.; Vederas, John C.

    2012-01-01

    Class IIa bacteriocins have been primarily explored as natural food preservatives, but there is much interest in exploring the application of these peptides as therapeutic antimicrobial agents. Bacteriocins of this class possess antimicrobial activity against several important human pathogens. Therefore, the therapeutic development of these bacteriocins will be reviewed. Biological and chemical modifications to both stabilize and increase the potency of bacteriocins are discussed, as well as the optimization of their production and purification. The suitability of bacteriocins as pharmaceuticals is explored through determinations of cytotoxicity, effects on the natural microbiota, and in vivo efficacy in mouse models. Recent results suggest that class IIa bacteriocins show promise as a class of therapeutic agents. PMID:22187559

  19. Sofosbuvir/velpatasvir: A promising combination

    PubMed Central

    Bonaventura, Aldo; Montecucco, Fabrizio

    2016-01-01

    Hepatitis C virus (HCV) affects 3% of the world population. It represents the main cause of chronic liver disease and is responsible for extra-hepatic complications, such as type 2 diabetes and cardiovascular diseases. HCV includes 7 genotypes differing in the nucleotide sequence variability, the geographic distribution, the rates of viral clearance, the risk of progression to liver fibrosis and to hepatocellular carcinoma, and the response to therapy. Last years have seen remarkable advances in the field of HCV infection with the approval of direct antiviral agents (DAAs) targeting key viral proteins involved in the HCV replication. Several oral regimens combining DAAs from different families have been developed and these regimens showed increased and sustained virological response rates to above 90% reducing the treatment duration to 12 wk or less. In particular, sofosbuvir, a nucleotide analogue nonstructural (NS)5B polymerase inhibitor, and velpatasvir, a NS5A inhibitor, have been tested in two phase 3 trials, the ASTRAL-2 (against HCV genotype 2) and the ASTRAL-3 (against HCV genotype 3), demonstrating to be effective, safe, and well tolerated in patients who were 18 years of age or older and had at least a 6-mo history of HCV infection with a compensated liver disease. PMID:27429714

  20. Sofosbuvir/velpatasvir: A promising combination.

    PubMed

    Bonaventura, Aldo; Montecucco, Fabrizio

    2016-07-01

    Hepatitis C virus (HCV) affects 3% of the world population. It represents the main cause of chronic liver disease and is responsible for extra-hepatic complications, such as type 2 diabetes and cardiovascular diseases. HCV includes 7 genotypes differing in the nucleotide sequence variability, the geographic distribution, the rates of viral clearance, the risk of progression to liver fibrosis and to hepatocellular carcinoma, and the response to therapy. Last years have seen remarkable advances in the field of HCV infection with the approval of direct antiviral agents (DAAs) targeting key viral proteins involved in the HCV replication. Several oral regimens combining DAAs from different families have been developed and these regimens showed increased and sustained virological response rates to above 90% reducing the treatment duration to 12 wk or less. In particular, sofosbuvir, a nucleotide analogue nonstructural (NS)5B polymerase inhibitor, and velpatasvir, a NS5A inhibitor, have been tested in two phase 3 trials, the ASTRAL-2 (against HCV genotype 2) and the ASTRAL-3 (against HCV genotype 3), demonstrating to be effective, safe, and well tolerated in patients who were 18 years of age or older and had at least a 6-mo history of HCV infection with a compensated liver disease. PMID:27429714

  1. Big data in nephrology: promises and pitfalls.

    PubMed

    Nadkarni, Girish N; Coca, Steven G; Wyatt, Christina M

    2016-08-01

    Data from the electronic health records hold great promise for nephrology research. However, due to significant limitations, reporting guidelines have been formulated for analyses conducted using electronic health records data. PMID:27418085

  2. Big data in nephrology: promises and pitfalls.

    PubMed

    Nadkarni, Girish N; Coca, Steven G; Wyatt, Christina M

    2016-08-01

    Data from the electronic health records hold great promise for nephrology research. However, due to significant limitations, reporting guidelines have been formulated for analyses conducted using electronic health records data.

  3. Innovative Trials Produce Promising Breast Cancer Drugs

    MedlinePlus

    ... news/fullstory_159762.html Innovative Trials Produce Promising Breast Cancer Drugs Adaptive study design allows researchers to match ... provide a fighting chance for women with advanced breast cancer. The drugs, neratinib and veliparib, both appear effective ...

  4. Panspermia: A Promising Field of Research

    NASA Astrophysics Data System (ADS)

    Rampelotto, P. H.

    2010-04-01

    In recent years, most of the major barriers against the acceptance of Panspermia have been demolished and this hypothesis emerges as a promising field of research. In this work, recent discoveries and the principal advances in Panspermia are discussed.

  5. Stem cell therapy in spinal cord injury: Hollow promise or promising science?

    PubMed Central

    Goel, Aimee

    2016-01-01

    Spinal cord injury (SCI) remains one of the most physically, psychologically and socially debilitating conditions worldwide. While rehabilitation measures may help limit disability to some extent, there is no effective primary treatment yet available. The efficacy of stem cells as a primary therapeutic option in spinal cord injury is currently an area under much scrutiny and debate. Several laboratory and some primary clinical studies into the use of bone marrow mesenchymal stem cells or embryonic stem cell-derived oligodentrocyte precursor cells have shown some promising results in terms of remyelination and regeneration of damaged spinal nerve tracts. More recently,laboratory and early clinical experiments into the use of Olfactory Ensheathing Cells, a type of glial cell derived from olfactory bulb and mucosa have provided some phenomenal preliminary evidence as to their neuroregenerative and neural bridging capacity. This report compares and evaluates some current research into selected forms of embryonic and mesenchymal stem cell therapy as well as olfactory ensheathing cell therapy in SCI, and also highlights some legal and ethical issues surrounding their use. While early results shows promise, more rigorous large scaleclinical trials are needed to shed light on the safety, efficacy and long term viability of stem cell and cellular transplant techniques in SCI. PMID:27217662

  6. Preparing Change Agents for Change Agent Roles.

    ERIC Educational Resources Information Center

    Sedlacek, James R.

    Seventy-seven Spanish- and Portuguese-speaking agricultural change agents from developing Central and South American countries responded to a questionnaire which sought perceptions of the roles in which the change agents felt they were involved and the roles for which they felt they were being trained. The agents were participating in training…

  7. Cold Atmospheric Plasma: A Promising Complementary Therapy for Squamous Head and Neck Cancer

    PubMed Central

    Welz, Christian; Emmert, Steffen; Canis, Martin; Becker, Sven; Baumeister, Philipp; Shimizu, Tetsuji; Morfill, Gregor E.; Harréus, Uli; Zimmermann, Julia L.

    2015-01-01

    Head and neck squamous cell cancer (HNSCC) is the 7th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP) presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD) plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay) and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viability for all tested treatment times (30, 60, 90, 120 and 180 s). IC 50 was reached within maximal 120 seconds of CAP treatment. Comet assay analysis showed a dose dependent high DNA fragmentation being one of the key players in anti-cancer activity of CAP. Annexin-V/PI staining revealed induction of apoptosis in CAP treated HNSCC cell lines but no significant dose dependency was seen. Thus, we confirmed that SMD Plasma technology is definitely a promising new approach on cancer treatment. PMID:26588072

  8. Cold Atmospheric Plasma: A Promising Complementary Therapy for Squamous Head and Neck Cancer.

    PubMed

    Welz, Christian; Emmert, Steffen; Canis, Martin; Becker, Sven; Baumeister, Philipp; Shimizu, Tetsuji; Morfill, Gregor E; Harréus, Uli; Zimmermann, Julia L

    2015-01-01

    Head and neck squamous cell cancer (HNSCC) is the 7th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP) presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD) plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay) and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viability for all tested treatment times (30, 60, 90, 120 and 180 s). IC 50 was reached within maximal 120 seconds of CAP treatment. Comet assay analysis showed a dose dependent high DNA fragmentation being one of the key players in anti-cancer activity of CAP. Annexin-V/PI staining revealed induction of apoptosis in CAP treated HNSCC cell lines but no significant dose dependency was seen. Thus, we confirmed that SMD Plasma technology is definitely a promising new approach on cancer treatment.

  9. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol.

    PubMed

    Della Badia, Laura A; Elshourbagy, Nabil A; Mousa, Shaker A

    2016-08-01

    Statins and other lipid-lowering drugs have dominated the market for many years for achievement of recommended levels of low-density lipoprotein cholesterol (LDL-C). However, a substantial number of high-risk patients are unable to achieve the LDL-C goal. Proprotein convertase subtilisin/kexin 9 (PCSK9) has recently emerged as a new, promising key therapeutic target for hypercholesterolemia. PCSK9 is a protease involved in chaperoning the low-density lipoprotein receptor to the process of degradation. PCSK9 inhibitors and statins effectively lower LDL-C. The PCSK9 inhibitors decrease the degradation of the LDL receptors, whereas statins mainly interfere with the synthetic machinery of cholesterol by inhibiting the key rate limiting enzyme, the HMG CoA reductase. PCSK9 inhibitors are currently being developed as monoclonal antibodies for their primary use in lowering LDL-C. They may be especially useful for patients with homozygous familial hypercholesterolemia, who at present receive minimal benefit from traditional statin therapy. The monoclonal antibody PCSK9 inhibitors, recently granted FDA approval, show the most promising safety and efficacy profile compared to other, newer LDL-C lowering therapies. This review will primarily focus on the safety and efficacy of monoclonal antibody PCSK9 inhibitors in comparison to statins. The review will also address new, alternative PCSK9 targeting drug classes such as small molecules, gene silencing agents, apolipoprotein B antisense oligonucleotides, and microsomal triglyceride transfer protein inhibitors.

  10. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol.

    PubMed

    Della Badia, Laura A; Elshourbagy, Nabil A; Mousa, Shaker A

    2016-08-01

    Statins and other lipid-lowering drugs have dominated the market for many years for achievement of recommended levels of low-density lipoprotein cholesterol (LDL-C). However, a substantial number of high-risk patients are unable to achieve the LDL-C goal. Proprotein convertase subtilisin/kexin 9 (PCSK9) has recently emerged as a new, promising key therapeutic target for hypercholesterolemia. PCSK9 is a protease involved in chaperoning the low-density lipoprotein receptor to the process of degradation. PCSK9 inhibitors and statins effectively lower LDL-C. The PCSK9 inhibitors decrease the degradation of the LDL receptors, whereas statins mainly interfere with the synthetic machinery of cholesterol by inhibiting the key rate limiting enzyme, the HMG CoA reductase. PCSK9 inhibitors are currently being developed as monoclonal antibodies for their primary use in lowering LDL-C. They may be especially useful for patients with homozygous familial hypercholesterolemia, who at present receive minimal benefit from traditional statin therapy. The monoclonal antibody PCSK9 inhibitors, recently granted FDA approval, show the most promising safety and efficacy profile compared to other, newer LDL-C lowering therapies. This review will primarily focus on the safety and efficacy of monoclonal antibody PCSK9 inhibitors in comparison to statins. The review will also address new, alternative PCSK9 targeting drug classes such as small molecules, gene silencing agents, apolipoprotein B antisense oligonucleotides, and microsomal triglyceride transfer protein inhibitors. PMID:27133571

  11. Cold Atmospheric Plasma: A Promising Complementary Therapy for Squamous Head and Neck Cancer.

    PubMed

    Welz, Christian; Emmert, Steffen; Canis, Martin; Becker, Sven; Baumeister, Philipp; Shimizu, Tetsuji; Morfill, Gregor E; Harréus, Uli; Zimmermann, Julia L

    2015-01-01

    Head and neck squamous cell cancer (HNSCC) is the 7th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP) presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD) plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay) and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viability for all tested treatment times (30, 60, 90, 120 and 180 s). IC 50 was reached within maximal 120 seconds of CAP treatment. Comet assay analysis showed a dose dependent high DNA fragmentation being one of the key players in anti-cancer activity of CAP. Annexin-V/PI staining revealed induction of apoptosis in CAP treated HNSCC cell lines but no significant dose dependency was seen. Thus, we confirmed that SMD Plasma technology is definitely a promising new approach on cancer treatment. PMID:26588072

  12. The Four Cs of Promising Practices in Community Colleges

    ERIC Educational Resources Information Center

    Haberler, Zachary; Levin, John S.

    2014-01-01

    To address the achievement or opportunity gap of underrepresented populations in community colleges, this qualitative field methods study investigated five California community college programs that have demonstrated progress in improving (or show significant potential to improve) student achievement. This research found that promising practices…

  13. Remote Agent Demonstration

    NASA Technical Reports Server (NTRS)

    Dorais, Gregory A.; Kurien, James; Rajan, Kanna

    1999-01-01

    We describe the computer demonstration of the Remote Agent Experiment (RAX). The Remote Agent is a high-level, model-based, autonomous control agent being validated on the NASA Deep Space 1 spacecraft.

  14. 46 CFR Sec. 2 - General Agent's requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false General Agent's requirements. Sec. 2 Section 2 Shipping... General Agent's requirements. The General Agent shall: (a) Obtain from the Master, a requisition for slop..., together with a copy of the vendor's invoice showing items, units, unit cost and totals. (c) Furnish...

  15. Acetylcholinesterase in Biofouling Species: Characterization and Mode of Action of Cyanobacteria-Derived Antifouling Agents.

    PubMed

    Almeida, Joana R; Freitas, Micaela; Cruz, Susana; Leão, Pedro N; Vasconcelos, Vitor; Cunha, Isabel

    2015-07-24

    Effective and ecofriendly antifouling (AF) compounds have been arising from naturally produced chemicals. The objective of this study is to use cyanobacteria-derived agents to investigate the role of acetylcholinesterase (AChE) activity as an effect and/or mode of action of promising AF compounds, since AChE inhibitors were found to inhibit invertebrate larval settlement. To pursue this objective, in vitro quantification of AChE activity under the effect of several cyanobacterial strain extracts as potential AF agents was performed along with in vivo AF (anti-settlement) screening tests. Pre-characterization of different cholinesterases (ChEs) forms present in selected tissues of important biofouling species was performed to confirm the predominance of AChE, and an in vitro AF test using pure AChE activity was developed. Eighteen cyanobacteria strains were tested as source of potential AF and AChE inhibitor agents. Results showed effectiveness in selecting promising eco-friendly AF agents, allowing the understanding of the AF biochemical mode of action induced by different compounds. This study also highlights the potential of cyanobacteria as source of AF agents towards invertebrate macrofouling species.

  16. Acetylcholinesterase in Biofouling Species: Characterization and Mode of Action of Cyanobacteria-Derived Antifouling Agents.

    PubMed

    Almeida, Joana R; Freitas, Micaela; Cruz, Susana; Leão, Pedro N; Vasconcelos, Vitor; Cunha, Isabel

    2015-08-01

    Effective and ecofriendly antifouling (AF) compounds have been arising from naturally produced chemicals. The objective of this study is to use cyanobacteria-derived agents to investigate the role of acetylcholinesterase (AChE) activity as an effect and/or mode of action of promising AF compounds, since AChE inhibitors were found to inhibit invertebrate larval settlement. To pursue this objective, in vitro quantification of AChE activity under the effect of several cyanobacterial strain extracts as potential AF agents was performed along with in vivo AF (anti-settlement) screening tests. Pre-characterization of different cholinesterases (ChEs) forms present in selected tissues of important biofouling species was performed to confirm the predominance of AChE, and an in vitro AF test using pure AChE activity was developed. Eighteen cyanobacteria strains were tested as source of potential AF and AChE inhibitor agents. Results showed effectiveness in selecting promising eco-friendly AF agents, allowing the understanding of the AF biochemical mode of action induced by different compounds. This study also highlights the potential of cyanobacteria as source of AF agents towards invertebrate macrofouling species. PMID:26213967

  17. Acetylcholinesterase in Biofouling Species: Characterization and Mode of Action of Cyanobacteria-Derived Antifouling Agents

    PubMed Central

    Almeida, Joana R.; Freitas, Micaela; Cruz, Susana; Leão, Pedro N.; Vasconcelos, Vitor; Cunha, Isabel

    2015-01-01

    Effective and ecofriendly antifouling (AF) compounds have been arising from naturally produced chemicals. The objective of this study is to use cyanobacteria-derived agents to investigate the role of acetylcholinesterase (AChE) activity as an effect and/or mode of action of promising AF compounds, since AChE inhibitors were found to inhibit invertebrate larval settlement. To pursue this objective, in vitro quantification of AChE activity under the effect of several cyanobacterial strain extracts as potential AF agents was performed along with in vivo AF (anti-settlement) screening tests. Pre-characterization of different cholinesterases (ChEs) forms present in selected tissues of important biofouling species was performed to confirm the predominance of AChE, and an in vitro AF test using pure AChE activity was developed. Eighteen cyanobacteria strains were tested as source of potential AF and AChE inhibitor agents. Results showed effectiveness in selecting promising eco-friendly AF agents, allowing the understanding of the AF biochemical mode of action induced by different compounds. This study also highlights the potential of cyanobacteria as source of AF agents towards invertebrate macrofouling species. PMID:26213967

  18. Preparation of near-infrared-labeled targeted contrast agents for clinical translation

    NASA Astrophysics Data System (ADS)

    Olive, D. Michael

    2011-03-01

    Targeted fluorophore-labeled contrast agents are moving toward translation to human surgical use. To prepare for future clinical use, we examined the performance of potential ligands targeting the epidermal growth factor receptor, α5β3 integrins, and GLUT transporters for their suitability as directed contrast agents. Each agent was labeled with IRDye 800CW, and near-infrared dye with excitation/emission wavelengths of 789/805 nm, which we determined had favorable toxicity characteristics. The probe molecules examined consisted of Affibodies, nanobodies, peptides, and the sugar 2-deoxy-D-glucose. Each probe was tested for specific and non-specific binding in cell based assays. All probe types showed good performance in mouse models for detecting either spontaneous tumors or tumor xenografts in vivo. Each of the probes tested show promise for future human clinical studies.

  19. PD-1 blockade therapy in renal cell carcinoma: current studies and future promises.

    PubMed

    Massari, F; Santoni, M; Ciccarese, C; Santini, D; Alfieri, S; Martignoni, G; Brunelli, M; Piva, F; Berardi, R; Montironi, R; Porta, C; Cascinu, S; Tortora, G

    2015-02-01

    RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Evasion of immune surveillance, a process defined immune-editing, leads to malignant progression. The striking improvement of knowledge in immunology has led to the identification of immune checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor immunity. The interaction between PD-1, an inducible inhibitory receptor expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells, results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1 axis inhibition by targeted-antibodies, increasing the T-cell proliferation and cytotoxicity, represents a promising mechanism to stimulate the anti-tumor activity of the immune system, improving the outcomes of cancer patients. Several PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing promising results. The interesting correlation between lymphocytes PD-1 expression and RCC advanced stage, grade and prognosis, as well as the selective PD-L1 expression by RCC tumor cells and its potential association with worse clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents, alone or in combination with anti-angiogenic drugs or other immunotherapeutic approaches, for the treatment of RCC. In this review we discuss the role of PD-1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies and promising therapeutic perspectives to target the PD-1 pathway.

  20. Enhanced sensitivity carbon nanotubes as targeted photoacoustic molecular imaging agents

    NASA Astrophysics Data System (ADS)

    de la Zerda, Adam; Liu, Zhuang; Zavaleta, Cristina; Bodapati, Sunil; Teed, Robert; Vaithilingam, Srikant; Ma, Te-Jen; Oralkan, Omer; Chen, Xiaoyuan; Khuri-Yakub, Butrus T.; Dai, Hongjie; Gambhir, Sanjiv S.

    2009-02-01

    Photoacoustic imaging of living subjects offers high spatial resolution at increased tissue depths compared to purely optical imaging techniques. We have recently shown that intravenously injected single walled carbon nanotubes (SWNTs) can be used as targeted photoacoustic imaging agents in living mice using RGD peptides to target αvβ3 integrins. We have now developed a new targeted photoacoustic imaging agent based on SWNTs and Indocyanine Green (SWNT-ICG) with absorption peak at 780nm. The photoacoustic signal of the new imaging agent is enhanced by ~20 times as compared to plain SWNTs. The particles are synthesized from SWNT-RGD that noncovalently attach to multiple ICG molecules through pi-pi stacking interactions. Negative control particles had RAD peptide instead of RGD. We measured the serum stability of the particles and verified that the RGD/RAD conjugation did not alter the particle's absorbance spectrum. Finally, through cell uptake studies with U87MG cells we verified that the particles bind selectively to αvβ3 integrin. In conclusion, the extremely high absorption of the SWNT-ICG particles shows great promise for high sensitivity photoacoustic imaging of molecular targets in-vivo. This work lays the foundations for future in-vivo studies that will use the SWNT-ICG particles as imaging agents administered systemically.

  1. Endogenizing geopolitical boundaries with agent-based modeling

    PubMed Central

    Cederman, Lars-Erik

    2002-01-01

    Agent-based modeling promises to overcome the reification of actors. Whereas this common, but limiting, assumption makes a lot of sense during periods characterized by stable actor boundaries, other historical junctures, such as the end of the Cold War, exhibit far-reaching and swift transformations of actors' spatial and organizational existence. Moreover, because actors cannot be assumed to remain constant in the long run, analysis of macrohistorical processes virtually always requires “sociational” endogenization. This paper presents a series of computational models, implemented with the software package REPAST, which trace complex macrohistorical transformations of actors be they hierarchically organized as relational networks or as collections of symbolic categories. With respect to the former, dynamic networks featuring emergent compound actors with agent compartments represented in a spatial grid capture organizational domination of the territorial state. In addition, models of “tagged” social processes allows the analyst to show how democratic states predicate their behavior on categorical traits. Finally, categorical schemata that select out politically relevant cultural traits in ethnic landscapes formalize a constructivist notion of national identity in conformance with the qualitative literature on nationalism. This “finite-agent method”, representing both states and nations as higher-level structures superimposed on a lower-level grid of primitive agents or cultural traits, avoids reification of agency. Furthermore, it opens the door to explicit analysis of entity processes, such as the integration and disintegration of actors as well as boundary transformations. PMID:12011409

  2. Bacteriocins as Potential Anticancer Agents

    PubMed Central

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies. PMID:26617524

  3. Bacteriocins as Potential Anticancer Agents.

    PubMed

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies.

  4. Therapeutic potential of chalcones as cardiovascular agents.

    PubMed

    Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar

    2016-03-01

    Cardiovascular diseases are the leading cause of death affecting 17.3 million people across the globe and are estimated to affect 23.3 million people by year 2030. In recent years, about 7.3 million people died due to coronary heart disease, 9.4 million deaths due to high blood pressure and 6.2 million due to stroke, where obesity and atherosclerotic progression remain the chief pathological factors. The search for newer and better cardiovascular agents is the foremost need to manage cardiac patient population across the world. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates to inhibit various cardiovascular, hematological and anti-obesity targets like angiotensin converting enzyme (ACE), cholesteryl ester transfer protein (CETP), diacylglycerol acyltransferase (DGAT), acyl-coenzyme A: cholesterol acyltransferase (ACAT), pancreatic lipase (PL), lipoprotein lipase (LPL), calcium (Ca(2+))/potassium (K(+)) channel, COX-1, TXA2 and TXB2. In this review, a comprehensive study of chalcones, their therapeutic targets, structure activity relationships (SARs), mechanisms of actions (MOAs) have been discussed. Chemically diverse chalcone scaffolds, their derivatives including structural manipulation of both aryl rings, replacement with heteroaryl scaffold(s) and hybridization through conjugation with other pharmacologically active scaffold have been highlighted. Chalcones which showed promising activity and have a well-defined MOAs, SARs must be considered as prototype for the design and development of potential anti-hypertensive, anti-anginal, anti-arrhythmic and cardioprotective agents. With the knowledge of these molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective chalcone derivatives as potential cardiovascular agents. PMID:26876916

  5. Biodegradation of novel amino acid derivatives suitable for complexing agents in pulp bleaching applications.

    PubMed

    Metsärinne, Sirpa; Ronkainen, Erja; Tuhkanen, Tuula; Aksela, Reijo; Sillanpää, Mika

    2007-05-01

    The biodegradability of four novel diethanolamine derivative complexing agents was examined by using two biodegradation tests standardised by OECD (301B and 301F). Ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were employed as reference substances. Biodegradation of the new complexing agents was studied both with unacclimated and acclimated inocula as well as by simulating wastewater treatment in sequencing batch reactors (SBRs). These new complexing agents were of technical grade, and therefore, the results are only indicative but these new compounds hold promise for use as complexing agents in the pulp and paper industry. The novel complexing agents were not readily biodegradable but they showed slight biodegradation. Around 10-30% degradation was found in the SBR where degradation was followed by measurement of concentration. Moreover the novel complexing agents did not have any negative impact on reactor performance as measured by chemical oxygen demand reduction. In the standardised biodegradation tests at best around 50% degradation was observed with the acclimated inoculum and in the prolonged test whereas EDTA and DTPA exhibited no biodegradation. The elevated degradation in acclimated sludge indicates that the water treatment plant microbes are capable of decomposing these molecules under favourable conditions. The total concentration of novel complexing agents decreased slightly during biodegradation tests, while the EDTA and DTPA concentrations remained stable. PMID:17346781

  6. Epigenetic Epidemiology: Promises for Public Health Research

    PubMed Central

    Bakulski, Kelly M.; Fallin, M. Daniele

    2014-01-01

    Epigenetic changes underlie developmental and age related biology. Promising epidemiologic research implicates epigenetics in disease risk and progression, and suggests epigenetic status depends on environmental risks as well as genetic predisposition. Epigenetics may represent a mechanistic link between environmental exposures, or genetics, and many common diseases, or may simply provide a quantitative biomarker for exposure or disease for areas of epidemiology currently lacking such measures. This great promise is balanced by issues related to study design, measurement tools, statistical methods, and biological interpretation that must be given careful consideration in an epidemiologic setting. This article describes the promises and challenges for epigenetic epidemiology, and suggests directions to advance this emerging area of molecular epidemiology. PMID:24449392

  7. Nursing science: more promise than threat.

    PubMed

    Jennings, B M

    1986-09-01

    This paper considers the issue of nursing science. Nursing, as an art, has long been accepted as integral to nursing. Nursing, as a science, however, is a more recent concept. Nursing science is viewed as a threat to the profession by its opponents, while the proponents of nursing science see it as a promise for advancement of the discipline. This paper examines the issue of nursing science by looking at its history and development, the definition of science, and five factors critical to the nursing science issue. The author concludes that nursing science is, in varying respects, both a threat and a promise. It is clear that the preponderance of evidence favours the promise nursing science holds for the profession of nursing. It is not a matter of choosing either art or science, but rather skillfully blending both for the betterment of nursing. Both art and science are necessary in nursing--neither, however, is sufficient.

  8. Development of Tc-99m Imaging Agents for Abeta Plaques

    SciTech Connect

    Zhi-Ping, Zhuang; Mei-Ping Kung; Catherihne Hou; Hank F. Kung

    2008-09-26

    Development of SPECT imaging agents based on Tc-99m targeting Aβ plaques is useful for diagnosis of Alzheimer’s disease (AD). A stilbene derivative, [11C]SB-13, showing promise in detecting senile plaques present in AD patients has been reported previously1,2. Based on the 4’-amino-stilbene core structure we have added substituted groups through which a chelating group, N2S2, was conjugated. We report herein a series of Tc-99m labeled stilbene derivative conjugated with a TcO[N2S2] core. The syntheses of stilbenes containing a N2S2 chelating ligand are achieved by a scheme shown. Lipophilic 99mTc stilbene complexes were successfully prepared and purified through HPLC. Preliminary results of in vitro labeling of brain sections from transgenic mice showed very promising plaque labeling. These 99mTc stilbene derivatives are warranted for further evaluations as potential imaging agents targeting amyloid plaques.

  9. Reversed field pinch: Progress and promise

    NASA Astrophysics Data System (ADS)

    Sprott, J. C.

    1985-05-01

    The Reversed Field Pinch (RFP) is a fusion reactor concept which, like the tokamak, confines the reacting plasma by the magnetic field produced in part by electrical currents flowing in the toroidally-confined plasma. Unlike the tokamak, the RFP requires very little externally-applied magnetic field, and thus offers the promise of a compact reactor with high power density which can be ohmically heated to ignition using non-superconducting magnet coils. Recent progress worldwide in RFP performance and physics understanding offers the promise of a new generation of devices which approach reactor conditions.

  10. Phytonutrients as therapeutic agents.

    PubMed

    Gupta, Charu; Prakash, Dhan

    2014-09-01

    Nutrients present in various foods plays an important role in maintaining the normal functions of the human body. The major nutrients present in foods include carbohydrates, proteins, lipids, vitamins, and minerals. Besides these, there are some bioactive food components known as "phytonutrients" that play an important role in human health. They have tremendous impact on the health care system and may provide medical health benefits including the prevention and/or treatment of disease and various physiological disorders. Phytonutrients play a positive role by maintaining and modulating immune function to prevent specific diseases. Being natural products, they hold a great promise in clinical therapy as they possess no side effects that are usually associated with chemotherapy or radiotherapy. They are also comparatively cheap and thus significantly reduce health care cost. Phytonutrients are the plant nutrients with specific biological activities that support human health. Some of the important bioactive phytonutrients include polyphenols, terpenoids, resveratrol, flavonoids, isoflavonoids, carotenoids, limonoids, glucosinolates, phytoestrogens, phytosterols, anthocyanins, ω-3 fatty acids, and probiotics. They play specific pharmacological effects in human health such as anti-microbial, anti-oxidants, anti-inflammatory, antiallergic, anti-spasmodic, anti-cancer, anti-aging, hepatoprotective, hypolipidemic, neuroprotective, hypotensive, diabetes, osteoporosis, CNS stimulant, analgesic, protection from UVB-induced carcinogenesis, immuno-modulator, and carminative. This mini-review attempts to summarize the major important types of phytonutrients and their role in promoting human health and as therapeutic agents along with the current market trend and commercialization.

  11. Promises and Challenges of Smac Mimetics as Cancer Therapeutics.

    PubMed

    Fulda, Simone

    2015-11-15

    Inhibitor of Apoptosis (IAP) proteins block programmed cell death and are expressed at high levels in various human cancers, thus making them attractive targets for cancer drug development. Second mitochondrial activator of caspases (Smac) mimetics are small-molecule inhibitors that mimic Smac, an endogenous antagonist of IAP proteins. Preclinical studies have shown that Smac mimetics can directly trigger cancer cell death or, even more importantly, sensitize tumor cells for various cytotoxic therapies, including conventional chemotherapy, radiotherapy, or novel agents. Currently, several Smac mimetics are under evaluation in early clinical trials as monotherapy or in rational combinations (i.e., GDC-0917/CUDC-427, LCL161, AT-406/Debio1143, HGS1029, and TL32711/birinapant). This review discusses the promise as well as some challenges at the translational interface of exploiting Smac mimetics as cancer therapeutics.

  12. Promising Practices in Instruction of Discovery Tools

    ERIC Educational Resources Information Center

    Buck, Stefanie; Steffy, Christina

    2013-01-01

    Libraries are continually changing to meet the needs of users; this includes implementing discovery tools, also referred to as web-scale discovery tools, to make searching library resources easier. Because these tools are so new, it is difficult to establish definitive best practices for teaching these tools; however, promising practices are…

  13. Behavioural activation: history, evidence and promise.

    PubMed

    Kanter, Jonathan W; Puspitasari, Ajeng J; Santos, Maria M; Nagy, Gabriela A

    2012-05-01

    Behavioural activation holds promise to reduce the global burden of depression as a treatment approach that is effective, easy to teach, scalable and acceptable to providers and patients across settings and cultures. This editorial reviews the history of behavioural activation, what it is, current evidence for its use and future directions.

  14. The Promise of Zoomable User Interfaces

    ERIC Educational Resources Information Center

    Bederson, Benjamin B.

    2011-01-01

    Zoomable user interfaces (ZUIs) have received a significant amount of attention in the 18 years since they were introduced. They have enjoyed some success, and elements of ZUIs are widely used in computers today, although the grand vision of a zoomable desktop has not materialised. This paper describes the premise and promise of ZUIs along with…

  15. Responses to Broken Promises: Does Personality Matter?

    ERIC Educational Resources Information Center

    Ho, Violet T.; Weingart, Laurie R.; Rousseau, Denise M.

    2004-01-01

    This paper examined the effects of personality traits on individuals' reactions to broken promises. We studied the effects of Neuroticism and Agreeableness on emotive and cognitive responses to breach and investigated whether these effects varied across different types (economic vs. social) and severity (high vs. low) of breach. We collected data…

  16. 76 FR 13152 - Promise Neighborhoods Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-10

    ... Neighborhoods strategies, these entities are at different stages of readiness to create a Promise Neighborhood... and implementation grants. The proposed priorities, requirements, and selection criteria are different... the Top notice inviting applications for new awards for FY 2010, 74 FR 59836, 59866 (November 18,...

  17. Promise in Action: Examples of Institutional Success

    ERIC Educational Resources Information Center

    Kuh, George D.

    2013-01-01

    In this article, the author illustrates how three campuses have, in their own way, attempted to bring coherence to the student experience and enrich that experience by more closely matching what was promised to what each student actually experiences while enrolled. Fulfilling students' expectations that were purposefully articulated in the mission…

  18. Student Teaching: Problems and Promising Practices.

    ERIC Educational Resources Information Center

    Griffin, Gary A., Ed.; Edwards, Sara, Ed.

    The working conference "Student Teaching: Problems and Promising Practices" brought together experts representing three different role orientations: cooperating teachers, school system representatives, and teacher educators. Under discussion was the student teaching process and the nature of research that might contribute to its better…

  19. Fulfilling the Promise of Educational Accountability

    ERIC Educational Resources Information Center

    Nelson, Sarah W.; McGhee, Marla W.; Meno, Lionel R.; Slater, Charles L.

    2007-01-01

    When No Child Left Behind (NCLB) was signed into law, the President and secretary of education promised sweeping reform of the American education system. In the five years since the law took effect, U.S. public schools have, indeed, seen remarkable change. However, not all of the changes have been well received. Policy makers, scholars, and…

  20. Exemplary & Promising Gender Equity Programs, 2000.

    ERIC Educational Resources Information Center

    Department of Education, Washington, DC.

    This report identifies promising and exemplary programs that promote gender equity in and through education during the 1996-99 Gender Equity Expert Panel review cycle. These programs need to meet four criteria: evidence of success/effectiveness in promoting gender equity, quality of program, educational significance, and usefulness to others or…

  1. The Promises of Moral Foundations Theory

    ERIC Educational Resources Information Center

    Musschenga, Bert

    2013-01-01

    In this article I examine whether Moral Foundations Theory can fulfil the promises that Haidt claims for the theory: that it will help in developing new approaches to moral education and to the moral conflicts that divide our diverse society. I argue that, first, the model that Haidt suggests for understanding the plurality of moralities--a shared…

  2. The promise of proteomics in animal science

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Proteomics hold significant promise as a method for advancing animal science research. The use of this technology in animal science is still in its infancy. The ability of proteomics to simultaneously identify and quantify potentially thousands of proteins is unparalleled. In this review, we will...

  3. Ideological Repositioning: Race, Social Justice, and Promise

    ERIC Educational Resources Information Center

    Hodge, Samuel R.

    2014-01-01

    In this paper, I engage in discourse centrally located in the ideology of race in the United States of America juxtaposed to social justice with promise for tomorrow in higher education and beyond. I assert that social justice in kinesiology requires that once hired, retaining, securing tenured status, and promoting faculty of color means having…

  4. Implementing Performance Assessment: Promises, Problems, and Challenges.

    ERIC Educational Resources Information Center

    Kane, Michael B., Ed.; Mitchell, Ruth, Ed.

    The chapters in this collection contribute to the debate about the value and usefulness of radically different kinds of assessments in the U.S. educational system by considering and expanding on the theoretical underpinnings of reports and speculation. The chapters are: (1) "Assessment Reform: Promises and Challenges" (Nidhi Khattri and David…

  5. Plan Showing Cross Bracing Under Upper Stringers, Typical Section Showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Plan Showing Cross Bracing Under Upper Stringers, Typical Section Showing End Framing, Plan Showing Cross Bracing Under Lower Stringers, End Elevation - Covered Bridge, Spanning Contoocook River, Hopkinton, Merrimack County, NH

  6. Network Analysis Shows Novel Molecular Mechanisms of Action for Copper-Based Chemotherapy

    PubMed Central

    Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique; Mejía, Carmen; Ruiz-Azuara, Lena

    2016-01-01

    The understanding of the mechanisms associated with the action of chemotherapeutic agents is fundamental to assess and account for possible side-effects of such treatments. Casiopeínas have demonstrated a cytotoxic effect by activation of pro-apoptotic processes in malignant cells. Such processes have been proved to activate the apoptotic intrinsic route, as well as cell cycle arrest. Despite this knowledge, the whole mechanism of action of Casiopeínas is yet to be completely understood. In this work we implement a systems biology approach based on two pathway analysis tools (Over-Representation Analysis and Causal Network Analysis) to observe changes in some hallmarks of cancer, induced by this copper-based chemotherapeutic agent in HeLa cell lines. We find that the metabolism of metal ions is exacerbated, as well as cell division processes being globally diminished. We also show that cellular migration and proliferation events are decreased. Moreover, the molecular mechanisms of liver protection are increased in the cell cultures under the actions of Casiopeínas, unlike the case in many other cytotoxic drugs. We argue that this chemotherapeutic agent may be promising, given its protective hepatic function, concomitant with its cytotoxic participation in the onset of apoptotic processes in malignant cells. PMID:26793116

  7. Pentamycin shows high efficacy against Trichomonas vaginalis.

    PubMed

    Kranzler, Markus; Syrowatka, Michael; Leitsch, David; Winnips, Cornelis; Walochnik, Julia

    2015-04-01

    Trichomonas vaginalis is the causative agent of the venereal disease trichomoniasis, which is the most frequent non-viral sexually transmitted disease worldwide. Since the 1960s, metronidazole has been the standard treatment, however an increasing number of cases with metronidazole-resistant strains is being reported. In this study, pentamycin, a polyene antibiotic, was tested for its in vitro efficacy against T. vaginalis using four strains with different metronidazole susceptibilities. It was shown that pentamycin is highly active against T. vaginalis and that the effect is prompt and independent of underlying metronidazole resistance. The effective concentrations (EC values) after 1 h of treatment were in the range 1.74-2.62 μg/mL (EC50) and 4.91-6.51 μg/mL (EC90). Total eradication of trichomonads (EC100) was achieved in all strains by treatment with 15 μg/mL (22 μM) for 1 h or with ≥1 μg/mL (≥1.5 μM) for 24 h. Long-term cultivation (12 months) under permanent drug pressure did not induce stable resistance against pentamycin in any of the strains tested. Pentamycin has been approved for intravaginal use and is a promising candidate for the topical treatment of trichomoniasis.

  8. Biological warfare agents.

    PubMed

    Pohanka, Miroslav; Kuca, Kamil

    2010-01-01

    Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents.

  9. Perfusion Imaging with a Freely Diffusible Hyperpolarized Contrast Agent

    PubMed Central

    Grant, Aaron K.; Vinogradov, Elena; Wang, Xiaoen; Lenkinski, Robert E.; Alsop, David C.

    2011-01-01

    Contrast agents that can diffuse freely into or within tissue have numerous attractive features for perfusion imaging. Here we present preliminary data illustrating the suitability of hyperpolarized 13C labeled 2-methylpropan-2-ol (also known as dimethylethanol, tertiary butyl alcohol and tert-butanol) as a freely diffusible contrast agent for magnetic resonance perfusion imaging. Dynamic 13C images acquired in rat brain with a balanced steady-state free precession (bSSFP) sequence following administration of hyperpolarized 2-methylpropan-2-ol show that this agent can be imaged with 2–4s temporal resolution, 2mm slice thickness, and 700 micron in-plane resolution while retaining adequate signal-to-noise ratio. 13C relaxation measurements on 2-methylpropan-2-ol in blood at 9.4T yield T1=46±4s and T2=0.55±0.03s. In the rat brain at 4.7T, analysis of the temporal dynamics of the bSSFP image intensity in tissue and venous blood indicate that 2-methylpropan-2-ol has a T2 of roughly 2–4s and a T1 of 43±24s. In addition, the images indicate that 2-methylpropan-2-ol is freely diffusible in brain and hence has a long residence time in tissue; this in turn makes it possible to image the agent continuously for tens of seconds. These characteristics show that 2-methylpropan-2-ol is a promising agent for robust and quantitative perfusion imaging in the brain and body. PMID:21432901

  10. Cyclotriazadisulfonamides: promising new CD4-targeted anti-HIV drugs.

    PubMed

    Vermeire, Kurt; Schols, Dominique

    2005-08-01

    It is imperative to continue efforts to identify novel effective therapies that can assist in containing the spread of HIV. Recently acquired knowledge about the HIV entry process points to new strategies to block viral entry. For most HIV strains, the successful infection of their target cells is mainly dependent on the presence of the CD4 surface molecule, which serves as the primary virus receptor. The attachment of the viral envelope to this cellular CD4 receptor can be considered as an ideal target with multiple windows of opportunity for therapeutic intervention. Therefore, drugs that interfere with the CD4 receptor, and thus inhibit viral entry, may be promising agents for the treatment of AIDS. The CD4-targeted HIV entry inhibitors cyclotriazadisulfonamides represent a novel class of small molecule antiviral agents with a unique mode of action. The lead compound, CADA, specifically interacts with the cellular CD4 receptor and is active against a wide variety of HIV strains at submicromolar levels when evaluated in different cell-types such as T cells, monocytes and dendritic cells. Moreover, a strict correlation has been demonstrated between anti-HIV activity and CD4 interaction of about 20 different CADA analogues. In addition, CADA acted synergistically in combination with all other FDA-approved anti-HIV drugs as well as with compounds that target the main HIV co-receptors. In this article, the characteristics of cyclotriazadisulfonamide compounds are presented and the possible application of CADA as a microbicide is also discussed. PMID:15980096

  11. Can propolis and caffeic acid phenethyl ester be promising agents against cyclophosphamide toxicity?

    PubMed Central

    Akyol, Sumeyya; Gulec, Mehmet Akif; Erdemli, Haci Kemal; Akyol, Omer

    2016-01-01

    Propolis is a mixture having hundreds of polyphenols including caffeic acid phenethyl ester (CAPE). They have been using in several medical conditions/diseases in both in vitro and in vivo experimental setup. Cyclophosphamide (CP) has been used to treat a broad of malignancies including Hodgkin’s and non-Hodgkin’s lymphoma, Burkitt’s lymphoma, chronic lymphocytic leukemia, Ewing’s sarcoma, breast cancer, testicular cancer, etc. It may cause several side effects after treatment. In this mini review, the protective effects of propolis and CAPE were compared each other in terms of effectiveness against CP-induced injuries. PMID:27069732

  12. Can propolis and caffeic acid phenethyl ester be promising agents against cyclophosphamide toxicity?

    PubMed

    Akyol, Sumeyya; Gulec, Mehmet Akif; Erdemli, Haci Kemal; Akyol, Omer

    2016-01-01

    Propolis is a mixture having hundreds of polyphenols including caffeic acid phenethyl ester (CAPE). They have been using in several medical conditions/diseases in both in vitro and in vivo experimental setup. Cyclophosphamide (CP) has been used to treat a broad of malignancies including Hodgkin's and non-Hodgkin's lymphoma, Burkitt's lymphoma, chronic lymphocytic leukemia, Ewing's sarcoma, breast cancer, testicular cancer, etc. It may cause several side effects after treatment. In this mini review, the protective effects of propolis and CAPE were compared each other in terms of effectiveness against CP-induced injuries. PMID:27069732

  13. Polyethylenimine mediated silver nanoparticle-decorated magnetic graphene as a promising photothermal antibacterial agent

    NASA Astrophysics Data System (ADS)

    Wang, Ning; Hu, Bo; Chen, Ming-Li; Wang, Jian-Hua

    2015-05-01

    A novel bactericidal material, Ag@rGO-Fe3O4-PEI composite is prepared by in situ growth of silver nanoparticles onto the polyethylenimine (PEI)-mediated magnetic reduced graphene oxide (GO). The antibacterial performances of the composite are investigated by using the gram-negative bacteria Escherichia coli O157:H7 (E. coli O157:H7) as a model. The results indicate that the Ag@rGO-Fe3O4-PEI composite exhibits excellent antibacterial performance against E. coli O157:H7, with an antibacterial performance superior to those for the ever-reported photothermal materials. The bactericidal capability or the inhibition capability for bacteria growth is found to depend on the dosage of the Ag@rGO-Fe3O4-PEI and Ag/rGO-Fe3O4-PEI mass ratio within a certain range. By using a dosage of 0.1 μg mL-1, a killing rate of 99.9% is achieved for the E. coli O157:H7 (1 × 107 cfu mL-1) under a 0.5 min NIR laser irradiation (785 nm/50 mW cm-2). In addition, a minimum bactericidal concentration (MBC) of 0.100 μg mL-1 is achieved under near infrared (NIR) laser irradiation for 10 min, for which case there is absolutely no colony of E. coli O157:H7 found in the broth agar plate.

  14. Computational Enzymology and Organophosphorus Degrading Enzymes: Promising Approaches Toward Remediation Technologies of Warfare Agents and Pesticides.

    PubMed

    Ramalho, Teodorico C; de Castro, Alexandre A; Silva, Daniela R; Silva, Maria Cristina; Franca, Tanos C C; Bennion, Brian J; Kuca, Kamil

    2016-01-01

    The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and help in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research.

  15. Biological Profile of Erucin: A New Promising Anticancer Agent from Cruciferous Vegetables

    PubMed Central

    Melchini, Antonietta; Traka, Maria H.

    2010-01-01

    Consumption of cruciferous vegetables has been associated with a reduced risk in the development of various types of cancer. This has been attributed to the bioactive hydrolysis products that are derived from these vegetables, namely isothiocyanates. Erucin is one such product derived from rocket salads, which is structurally related to sulforaphane, a well-studied broccoli-derived isothiocyanate. In this review, we present current knowledge on mechanisms of action of erucin in chemoprevention obtained from cell and animal models and relate it to other isothiocyanates. These mechanisms include modulation of phase I, II and III detoxification, regulation of cell growth by induction of apoptosis and cell cycle arrest, induction of ROS-mechanisms and regulation androgen receptor pathways. PMID:22069601

  16. “Silymarin”, a Promising Pharmacological Agent for Treatment of Diseases

    PubMed Central

    Karimi, Gholamreza; Vahabzadeh, Maryam; Lari, Parisa; Rashedinia, Marziyeh; Moshiri, Mohammad

    2011-01-01

    Widespread use of herbal drugs because of their protective effects on different organs toxicity has been shown in many studies. These protective effects have been illustrated in the fields of nephrotoxicity, hepatotoxicity, viral hepatitis, cancer, in vitro fertilization, neurotoxicity, depression, lung diseases, prostate diseases etc. Silymarin has cytoprotection activities due to its antioxidant activity and radical scavenging. The possible known mechanisms of action of silymarin protection are blockade and adjustment of cell transporters, p-glycoprotein, estrogenic and nuclear receptors. Moreover, silymarin anti-inflammatory effects through reduction of TNF-α, protective effects on erythrocyte lysis and cisplatin-induced acute nephrotoxicity have been indicated in some studies. Silymarin has also inhibited apoptosis and follicular development in patients undergoing IVF. Basis on such data, silymarin can be served as a novel medication in complementary medicine. PMID:23492971

  17. Mitomycin C: a promising agent for the treatment of canine corneal scarring

    PubMed Central

    Gupta, Rangan; Yarnall, Benjamin W.; Giuliano, Elizabeth A.; Kanwar, Jagat R.; Buss, Dylan G.; Mohan, Rajiv R.

    2012-01-01

    Objective To evaluate the safety and efficacy of mitomycin C (MMC) in prevention of canine corneal scarring. Methods With an in vitro approach using healthy canine corneas, cultures of primary canine corneal fibroblasts or myofibroblasts were generated. Primary canine corneal fibroblasts were obtained by growing corneal buttons in minimal essential medium supplemented with 10% fetal bovine serum. Canine corneal myofibroblasts were produced by growing cultures in serum-free medium containing transforming growth factor β1 (1 ng/mL). Trypan blue assay and phase-contrast microscopy were used to evaluate the toxicity of three doses of MMC (0.002%, 0.02% and 0.04%). Real-time PCR, immunoblot, and immunocytochemistry techniques were used to determine MMC efficacy to inhibit markers of canine corneal scarring. Results A single 2-min treatment of 0.02% or less MMC did not alter canine corneal fibroblast or keratocyte phenotype, viability, or growth. The 0.02% dose substantially reduced myofibroblast formation (up to 67%; P < 0.001), as measured by the change in RNA and protein expression of fibrosis biomarkers (α-smooth muscle actin and F-actin). Conclusion This in vitro study suggests that a single 2-min 0.02% MMC treatment to the canine corneal keratocytes is safe and may be useful in decreasing canine corneal fibrous metaplasia. In vivo studies are warranted. PMID:21929607

  18. Computational Enzymology and Organophosphorus Degrading Enzymes: Promising Approaches Toward Remediation Technologies of Warfare Agents and Pesticides.

    PubMed

    Ramalho, Teodorico C; de Castro, Alexandre A; Silva, Daniela R; Silva, Maria Cristina; Franca, Tanos C C; Bennion, Brian J; Kuca, Kamil

    2016-01-01

    The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and help in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research. PMID:26898655

  19. Polyethylenimine mediated silver nanoparticle-decorated magnetic graphene as a promising photothermal antibacterial agent.

    PubMed

    Wang, Ning; Hu, Bo; Chen, Ming-Li; Wang, Jian-Hua

    2015-05-15

    A novel bactericidal material, Ag@rGO-Fe3O4-PEI composite is prepared by in situ growth of silver nanoparticles onto the polyethylenimine (PEI)-mediated magnetic reduced graphene oxide (GO). The antibacterial performances of the composite are investigated by using the gram-negative bacteria Escherichia coli O157:H7 (E. coli O157:H7) as a model. The results indicate that the Ag@rGO-Fe3O4-PEI composite exhibits excellent antibacterial performance against E. coli O157:H7, with an antibacterial performance superior to those for the ever-reported photothermal materials. The bactericidal capability or the inhibition capability for bacteria growth is found to depend on the dosage of the Ag@rGO-Fe3O4-PEI and Ag/rGO-Fe3O4-PEI mass ratio within a certain range. By using a dosage of 0.1 μg mL(-1), a killing rate of 99.9% is achieved for the E. coli O157:H7 (1 × 10(7) cfu mL(-1)) under a 0.5 min NIR laser irradiation (785 nm/50 mW cm(-2)). In addition, a minimum bactericidal concentration (MBC) of 0.100 μg mL(-1) is achieved under near infrared (NIR) laser irradiation for 10 min, for which case there is absolutely no colony of E. coli O157:H7 found in the broth agar plate.

  20. Sodium hypochlorite: A promising agent for reducing Botrytis cinerea infection on rose flowers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Botrytis cinerea is a fungal pathogen that greatly reduces the postharvest quality of rose flowers. We determined the potential of sodium hypochlorite (NaOCl), an oxidizer with antimicrobial activity, to reduce the incidence of disease on flowers. A postharvest dip in 200 µL L-1 NaOCl for 10 s at ...

  1. Gold nanoparticles as novel agents for cancer therapy

    PubMed Central

    Jain, S; Hirst, D G; O'Sullivan, J M

    2012-01-01

    Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed. PMID:22010024

  2. Agent-based forward analysis

    SciTech Connect

    Kerekes, Ryan A.; Jiao, Yu; Shankar, Mallikarjun; Potok, Thomas E.; Lusk, Rick M.

    2008-01-01

    We propose software agent-based "forward analysis" for efficient information retrieval in a network of sensing devices. In our approach, processing is pushed to the data at the edge of the network via intelligent software agents rather than pulling data to a central facility for processing. The agents are deployed with a specific query and perform varying levels of analysis of the data, communicating with each other and sending only relevant information back across the network. We demonstrate our concept in the context of face recognition using a wireless test bed comprised of PDA cell phones and laptops. We show that agent-based forward analysis can provide a significant increase in retrieval speed while decreasing bandwidth usage and information overload at the central facility. n

  3. A dual function theranostic agent for near-infrared photoacoustic imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Upputuri, Paul Kumar; Huang, Shuo; Wang, Mingfeng; Pramanik, Manojit

    2016-03-01

    Theranostic, defined as combining diagnostic and therapeutic agents, has attracted more attention in biomedical application. It is essential to monitor diseased tissue before treatment. Photothermal therapy (PTT) is a promising treatment of cancer tissue due to minimal invasion, unharmful to normal tissue and high efficiency. Photoacoustic tomography (PAT) is a hybrid nonionizing biomedical imaging modality that combines rich optical contrast and high ultrasonic resolution in a single imaging modality. The near infra-red (NIR) wavelengths, usually used in PAT, can provide deep penetration at the expense of reduced contrast, as the blood absorption drops in the NIR range. Exogenous contrast agents with strong absorption in the NIR wavelength range can enhance the photoacoustic imaging contrast as well as imaging depth. Most theranostic agents incorporating PAT and PTT are inorganic nanomaterials that suffer from poor biocompatibility and biodegradability. Herein, we present an benzo[1,2-c;4,5-c'] bis[1,2,5] thiadiazole (BBT), based theranostic agent which not only acts as photoacoustic contrast agent but also a photothermal therapy agent. Experiments were performed on animal blood and organic nanoparticles embedded in a chicken breast tissue using PAT imaging system at ~803 nm wavelengths. Almost ten time contrast enhancement was observed from the nanoparticle in suspension. More than 6.5 time PA signal enhancement was observed in tissue at 3 cm depth. HeLa cell lines was used to test photothermal effect showing 90% cells were killed after 10 min laser irradiation. Our results indicate that the BBT - based naoparticles are promising theranostic agents for PAT imaging and cancer treatment by photothermal therapy.

  4. A class of promising acaricidal tetrahydroisoquinoline derivatives: synthesis, biological evaluation and structure-activity relationships.

    PubMed

    Yang, Rui; Ruan, Qiao; Zhang, Bing-Yu; Zheng, Zuo-Lue; Miao, Fang; Zhou, Le; Geng, Hui-Ling

    2014-01-01

    As part of our continuing research on isoquinoline acaricidal drugs, this paper reports the preparation of a series of the 2-aryl-1-cyano-1,2,3,4-tetrahydroisoquinolines with various substituents on the N-phenyl ring, their in vitro acaricidal activities against Psoroptes cuniculi, a mange mite, and discusses their SAR as well. The structures of all compounds, including 12 new ones, were elucidated by analysis of UV, IR, NMR, ESI-MS, HR-MS spectra and X-ray diffraction experiments. All target compounds showed varying degrees of activity at 0.4 mg/mL. Compound 1 showed the strongest activity, with a 50% lethal concentration value (LC50) of 0.2421 μg/mL and 50% lethal time value (LT50) of 7.79 h, comparable to the standard drug ivermectin (LC50 = 0.2474 μg/mL; LT50 = 20.9 h). The SAR showed that the substitution pattern on the N-aromatic ring exerted a significant effect on the activity. The substituents 2'-F, 3'-F, 2'-Cl, 2'-Br and 2'-CF3 remarkably enhanced the activity. Generally, for the isomers with the same substituents at different positions, the order of the activity was ortho > meta > para. It was concluded that the target compounds represent a class of novel promising candidates or lead compounds for the development of new tetrahydroisoquinoline acaricidal agents.

  5. Biocompatible KMnF3 nanoparticular contrast agent with proper plasma retention time for in vivo magnetic resonance imaging.

    PubMed

    Liu, Zhi-jun; Song, Xiao-xia; Xu, Xian-zhu; Tang, Qun

    2014-04-18

    Nanoparticular MRI contrast agents are rapidly becoming suitable for use in clinical diagnosis. An ideal nanoparticular contrast agent should be endowed with high relaxivity, biocompatibility, proper plasma retention time, and tissue-specific or tumor-targeting imaging. Herein we introduce PEGylated KMnF3 nanoparticles as a new type of T1 contrast agent. Studies showed that the nanoparticular contrast agent revealed high bio-stability with bovine serum albumin in PBS buffer solution, and presented excellent biocompatibility (low cytotoxicity, undetectable hemolysis and hemagglutination). Meanwhile the new contrast agent possessed proper plasma retention time (circulation half-life t1/2 is approximately 2 h) in the body of the administrated mice. It can be delivered into brain vessels and maintained there for hours, and is mostly cleared from the body within 48 h, as demonstrated by time-resolved MRI and Mn-biodistribution analysis. Those distinguishing features make it suitable to obtain contrast-enhanced brain magnetic resonance angiography. Moreover, through the process of passive targeting delivery, the T1 contrast agent clearly illuminates a brain tumor (glioma) with high contrast image and defined shape. This study demonstrates that PEGylated KMnF3 nanoparticles represent a promising biocompatible vascular contrast agent for magnetic resonance angiography and can potentially be further developed into an active targeted tumor MRI contrast agent.

  6. Biocompatible KMnF3 nanoparticular contrast agent with proper plasma retention time for in vivo magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Liu, Zhi-jun; Song, Xiao-xia; Xu, Xian-zhu; Tang, Qun

    2014-04-01

    Nanoparticular MRI contrast agents are rapidly becoming suitable for use in clinical diagnosis. An ideal nanoparticular contrast agent should be endowed with high relaxivity, biocompatibility, proper plasma retention time, and tissue-specific or tumor-targeting imaging. Herein we introduce PEGylated KMnF3 nanoparticles as a new type of T1 contrast agent. Studies showed that the nanoparticular contrast agent revealed high bio-stability with bovine serum albumin in PBS buffer solution, and presented excellent biocompatibility (low cytotoxicity, undetectable hemolysis and hemagglutination). Meanwhile the new contrast agent possessed proper plasma retention time (circulation half-life t1/2 is approximately 2 h) in the body of the administrated mice. It can be delivered into brain vessels and maintained there for hours, and is mostly cleared from the body within 48 h, as demonstrated by time-resolved MRI and Mn-biodistribution analysis. Those distinguishing features make it suitable to obtain contrast-enhanced brain magnetic resonance angiography. Moreover, through the process of passive targeting delivery, the T1 contrast agent clearly illuminates a brain tumor (glioma) with high contrast image and defined shape. This study demonstrates that PEGylated KMnF3 nanoparticles represent a promising biocompatible vascular contrast agent for magnetic resonance angiography and can potentially be further developed into an active targeted tumor MRI contrast agent.

  7. Synthesis and biological evaluation of hydrazone derivatives as antifungal agents.

    PubMed

    Casanova, Bruna B; Muniz, Mauro N; de Oliveira, Thayse; de Oliveira, Luís Flavio; Machado, Michel M; Fuentefria, Alexandre M; Gosmann, Grace; Gnoatto, Simone C B

    2015-05-20

    Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16-32 μg/mL and 8-16 μg/mL, respectively. The compounds' action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents.

  8. Promise of cancer stem cell vaccine

    PubMed Central

    Zhou, Li; Lu, Lin; Wicha, Max S; Chang, Alfred E; Xia, Jian-chuan; Ren, Xiubao; Li, Qiao

    2015-01-01

    Dendritic cell (DC)-based vaccines designed to target cancer stem cells (CSC) can induce significant antitumor responses via conferring host anti-CSC immunity. Our recent studies have demonstrated that CSC-DC vaccine could inhibit metastasis of primary tumors and induce humoral immune responses against cancer stem cells. This approach highlights the promise of cancer stem cell vaccine in cancer immunotherapy. PMID:26337078

  9. Putative neuroprotective agents in neuropsychiatric disorders.

    PubMed

    Dodd, Seetal; Maes, Michael; Anderson, George; Dean, Olivia M; Moylan, Steven; Berk, Michael

    2013-04-01

    In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders.

  10. Anti-aging pharmacology: Promises and pitfalls.

    PubMed

    Vaiserman, Alexander M; Lushchak, Oleh V; Koliada, Alexander K

    2016-11-01

    Life expectancy has grown dramatically in modern times. This increase, however, is not accompanied by the same increase in healthspan. Efforts to extend healthspan through pharmacological agents targeting aging-related pathological changes are now in the spotlight of geroscience, the main idea of which is that delaying of aging is far more effective than preventing the particular chronic disorders. Currently, anti-aging pharmacology is a rapidly developing discipline. It is a preventive field of health care, as opposed to conventional medicine which focuses on treating symptoms rather than root causes of illness. A number of pharmacological agents targeting basic aging pathways (i.e., calorie restriction mimetics, autophagy inducers, senolytics etc.) are now under investigation. This review summarizes the literature related to advances, perspectives and challenges in the field of anti-aging pharmacology. PMID:27524412

  11. Anti-aging pharmacology: Promises and pitfalls.

    PubMed

    Vaiserman, Alexander M; Lushchak, Oleh V; Koliada, Alexander K

    2016-11-01

    Life expectancy has grown dramatically in modern times. This increase, however, is not accompanied by the same increase in healthspan. Efforts to extend healthspan through pharmacological agents targeting aging-related pathological changes are now in the spotlight of geroscience, the main idea of which is that delaying of aging is far more effective than preventing the particular chronic disorders. Currently, anti-aging pharmacology is a rapidly developing discipline. It is a preventive field of health care, as opposed to conventional medicine which focuses on treating symptoms rather than root causes of illness. A number of pharmacological agents targeting basic aging pathways (i.e., calorie restriction mimetics, autophagy inducers, senolytics etc.) are now under investigation. This review summarizes the literature related to advances, perspectives and challenges in the field of anti-aging pharmacology.

  12. Radiopharmaceuticals in PET, Progress and Promise

    DOE R&D Accomplishments Database

    Wolf, A. P.; Fowler, J. S.

    1988-11-01

    It is the intention of this presentation to focus on the current state of radiopharmaceuticals for PET and where this is leading us. PET radiopharmaceuticals can be broken down into perhaps seven categories at present with each being applicable to a different aspect of human biochemistry. These are: metabolic probes, neurochemical probes, enzyme probes, ion channel blockers, blood flow agents, ethical drugs and other positron emitters.

  13. Radiopharmaceuticals in PET, progress and promise

    SciTech Connect

    Wolf, A.P.; Fowler, J.S.

    1988-11-01

    It is the intention of this presentation to focus on the current state of radiopharmaceuticals for PET and where this is leading us. PET radiopharmaceuticals can be broken down into perhaps seven categories at present with each being applicable to a different aspect of human biochemistry. These are: metabolic probes, neurochemical probes, enzyme probes, ion channel blockers, blood flow agents, ethical drugs and other positron emitters. 7 refs.

  14. Natural Antioxidants and Hypertension: Promise and Challenges

    PubMed Central

    Kizhakekuttu, Tinoy J.; Widlansky, Michael E.

    2010-01-01

    Hypertension reigns as a leading cause of cardiovascular morbidity and mortality worldwide. Excessive reactive oxygen species (ROS) has emerged as a central common pathway by which disparate influences may induce and exacerbate hypertension. Potential sources of excessive ROS in hypertension include NADPH oxidase, mitochondria, xanthine oxidase, endothelium-derived NO synthase (eNOS), cyclooxygenase 1 and 2, cytochrome P450 epoxygenase and transition metals. While a significant body of epidemiological and clinical data suggests that antioxidant rich diets reduce blood pressure and cardiovascular risk, randomized trials and population studies using natural antioxidants have yielded disappointing results. The reasons behind this lack of efficacy are not completely clear, but likely include a combination of 1) ineffective dosing regimens 2) the potential pro-oxidant capacity of some of these agents 3) selection of subjects less likely to benefit from antioxidant therapy (too healthy or too sick), 4) inefficiency of non-specific quenching of prevalent ROS versus prevention of excessive ROS production. Commonly used antioxidants include Vitamins A, C and E, L-arginine, flavanoids, and mitochondria targeted agents, Coenzyme Q10, acetyl-L-carnitine and alpha-lipoic acid. Various reasons, including incomplete knowledge of the mechanisms of action of these agents, lack of target specificity, and potential inter-individual differences in therapeutic efficacy preclude us from recommending any specific natural antioxidant for antihypertensive therapy at this time. This review focuses on recent literature regarding above mentioned issues evaluating naturally occurring antioxidants with respect to their impact on hypertension. PMID:20370791

  15. Mechanisms of DNA methyltransferase-inhibitor interactions: Procyanidin B2 shows new promise for therapeutic intervention of cancer.

    PubMed

    Shilpi, Arunima; Parbin, Sabnam; Sengupta, Dipta; Kar, Swayamsiddha; Deb, Moonmoon; Rath, Sandip Kumar; Pradhan, Nibedita; Rakshit, Madhumita; Patra, Samir Kumar

    2015-05-25

    DNA methyltransferases (DNMTs) is a key epigenetic enzyme for pharmacological manipulation and is employed in cancer reprogramming. During past few years multiple strategies have been implemented to excavate epigenetic compounds targeting DNMTs. In light of the emerging concept of chemoinformatics, molecular docking and simulation studies have been employed to accelerate the development of DNMT inhibitors. Among the DNMT inhibitors known till date, epigallocathechin-3-gallate (EGCG) was identified to be effective in reducing DNMT activity. However, the broad spectrum of EGCG to other diseases and variable target enzymes offers some limitations. In view of this, 32 EGCG analogues were screened at S-Adnosyl-L-homocysteine (SAH) binding pocket of DNMTs and procyanidin B2-3, 3'-di-O-gallate (procyanidin B2) was obtained as potent inhibitor having medicinally relevant chemical space. Further, in vitro analysis demonstrates the efficiency of procyanidin B2 in attenuating DNMT activity at IC50 of 6.88±0.647 μM and subsequently enhancing the expression of DNMT target genes, E-cadherin, Maspin and BRCA1. Moreover, the toxic property of procyanidin B2 towards triple negative breast cancer cells to normal cells offers platform for pre-clinical trial and an insight to the treatment of cancer.

  16. Extremophile extracts and enhancement techniques show promise for the development of a live vaccine against Flavobacterium columnare

    USGS Publications Warehouse

    Powell, D.B.; Palm, R.C.; MacKenzie, A.P.; Winton, J.R.

    2009-01-01

    The effects of temperature, ionic strength, and new cryopreservatives derived from polar ice bacteria were investigated to help accelerate the development of economical, live attenuated vaccines for aquaculture. Extracts of the extremophile Gelidibacter algens functioned very well as part of a lyophilization cryoprotectant formulation in a 15-week storage trial. The bacterial extract and trehalose additives resulted in significantly higher colony counts of columnaris bacteria (Flavobacterium columnare) compared to nonfat milk or physiological saline at all time points measured. The bacterial extract combined with trehalose appeared to enhance the relative efficiency of recovery and growth potential of columnaris in flask culture compared to saline, nonfat milk, or trehalose-only controls. Pre-lyophilization temperature treatments significantly affected F. columnare survival following rehydration. A 30-min exposure at 0 ??C resulted in a 10-fold increase in bacterial survival following rehydration compared to mid-range temperature treatments. The brief 30 and 35 ??C pre-lyophilization exposures appeared to be detrimental to the rehydration survival of the bacteria. The survival of F. columnare through the lyophilization process was also strongly affected by changes in ionic strength of the bacterial suspension. Changes in rehydration constituents were also found to be important in promoting increased survival and growth. As the sodium chloride concentration increased, the viability of rehydrated F. columnare decreased. ?? 2009 Elsevier Inc.

  17. A collaborative accountable care model in three practices showed promising early results on costs and quality of care.

    PubMed

    Salmon, Richard B; Sanderson, Mark I; Walters, Barbara A; Kennedy, Karen; Flores, Robert C; Muney, Alan M

    2012-11-01

    Cigna's Collaborative Accountable Care initiative provides financial incentives to physician groups and integrated delivery systems to improve the quality and efficiency of care for patients in commercial open-access benefit plans. Registered nurses who serve as care coordinators employed by participating practices are a central feature of the initiative. They use patient-specific reports and practice performance reports provided by Cigna to improve care coordination, identify and close care gaps, and address other opportunities for quality improvement. We report interim quality and cost results for three geographically and structurally diverse provider practices in Arizona, New Hampshire, and Texas. Although not statistically significant, these early results revealed favorable trends in total medical costs and quality of care, suggesting that a shared-savings accountable care model and collaborative support from the payer can enable practices to take meaningful steps toward full accountability for care quality and efficiency.

  18. Hydrophobic dipeptide crystals: a promising Ag-free class of ultramicroporous materials showing argon/oxygen adsorption selectivity.

    PubMed

    Afonso, R; Mendes, A; Gales, L

    2014-09-28

    The adsorption isotherms of nitrogen, oxygen and argon in four VA-class hydrophobic dipeptides are presented. Isotherms were determined at 5, 20 and 35 °C, for a pressure range of 0-6 bar. Under these conditions, adsorption is still in the Henry region. For all materials and temperatures, the sequence of preferential adsorption is Ar > O2 > N2, a highly abnormal result. At 5 °C, the dipeptide with the smallest pores, VI, has Ar/O2 adsorption equilibrium selectivities up to 1.30, the highest ever measured in Ag-free adsorbents. Gas uptakes, at 1 bar and 20 °C, are ∼0.05 mol kg(-1), very low relative values that are partially explained by the low porosity of the solids (<10%). The significance of these results for the development of new materials for the process of O2 generation by pressure swing adsorption (PSA) is discussed. The results indicate some of the structural and chemical properties that prospective Ag-free adsorbents should have in order to have Ar/O2 selectivity, hydrophobic pores, less than 0.5 nm-wide, and porosity of, at least, 20%.

  19. New hybrids from peanut (Arachis hypogaea L.) and synthetic amphidiploid crosses show promise in increasing pest and disease tolerance.

    PubMed

    Fávero, A P; Pádua, J G; Costa, T S; Gimenes, M A; Godoy, I J; Moretzsohn, M C; Michelotto, M D

    2015-12-11

    The primary gene pool of the cultivated peanut (Arachis hypogaea L., allotetraploid AABB) is very narrow for some important characteristics, such as resistance to pests and diseases. However, the Arachis wild diploid species, particularly those from the section Arachis, still have these characteristics. To improve peanut crops, genes from the wild species can be introgressed by backcrossing the hybrids with A. hypogaea. When diploid species whose genomes are similar to those of the cultivated peanut are crossed, sterile hybrids result. Artificially doubling the number of chromosomes of these hybrids results in fertile synthetic polyploids. The objectives of this study were: 1) to obtain progenies by crossing amphidiploids with the cultivated peanut, and 2) to characterize these two groups of materials (amphidiploids and progenies) so that they may be efficiently conserved and used. Using morphological, molecular, and pollen viability descriptors we evaluated one cultivar of A. hypogaea (IAC 503), eight synthetic amphidiploids, and the progenies resulting from four distinct combinations of crossing between IAC 503 and four amphidiploids.

  20. Chemical warfare agents.

    PubMed

    Chauhan, S; Chauhan, S; D'Cruz, R; Faruqi, S; Singh, K K; Varma, S; Singh, M; Karthik, V

    2008-09-01

    Chemical warfare agents (CWA's) are defined as any chemical substance whose toxic properties are utilised to kill, injure or incapacitate an enemy in warfare and associated military operations. Chemical agents have been used in war since times immemorial, but their use reached a peak during World War I. During World War II only the Germans used them in the infamous gas chambers. Since then these have been intermittently used both in war and acts of terrorisms. Many countries have stockpiles of these agents. There has been a legislative effort worldwide to ban the use of CWA's under the chemical weapons convention which came into force in 1997. However the manufacture of these agents cannot be completely prohibited as some of them have potential industrial uses. Moreover despite the remedial measures taken so far and worldwide condemnation, the ease of manufacturing these agents and effectiveness during combat or small scale terrorist operations still make them a powerful weapon to reckon with. These agents are classified according to mechanism of toxicity in humans into blister agents, nerve agents, asphyxiants, choking agents and incapacitating/behavior altering agents. Some of these agents can be as devastating as a nuclear bomb. In addition to immediate injuries caused by chemical agents, some of them are associated with long term morbidities and psychological problems. In this review we will discuss briefly about the historical background, properties, manufacture techniques and industrial uses, mechanism of toxicity, clinical features of exposure and pharmacological management of casualties caused by chemical agents. PMID:21783898

  1. Arylthiosemicarbazones as antileishmanial agents.

    PubMed

    Manzano, José Ignacio; Cochet, Florent; Boucherle, Benjamin; Gómez-Pérez, Verónica; Boumendjel, Ahcène; Gamarro, Francisco; Peuchmaur, Marine

    2016-11-10

    Based on a screening process, we targeted substituted thiosemicarbazone as potential antileishmanial agents. Our objective was to identify the key structural elements contributing to the anti-parasite activity that might be used for development of effective drugs. A series of 32 compounds was synthesized and their efficacy was evaluated against the clinically relevant intracellular amastigotes of Leishmania donovani. From these, 22 compounds showed EC50 values below 10 μM with the most active derivative (compound 14) showing an EC50 of 0.8 μM with very low toxicity on two different mammalian cell lines. The most relevant structural elements required for higher activity indicate that the presence of a fused bicyclic aromatic ring such as a naphthalene bearing an alkyl or an alkoxy group substituent are prerequisites. Owing to the easy synthesis, high activity and low toxicity, the most active compounds could be considered as a lead for further development.

  2. Proceedings of the Agent 2002 Conference on Social Agents : Ecology, Exchange, and Evolution

    SciTech Connect

    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 the ''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.

  3. Safe motion planning for mobile agents: A model of reactive planning for multiple mobile agents

    SciTech Connect

    Fujimura, Kikuo.

    1990-01-01

    The problem of motion planning for multiple mobile agents is studied. Each planning agent independently plans its own action based on its map which contains a limited information about the environment. In an environment where more than one mobile agent interacts, the motions of the robots are uncertain and dynamic. A model for reactive agents is described and simulation results are presented to show their behavior patterns. 18 refs., 2 figs.

  4. Functionalized-MnO2/chitosan nanocomposites: A promising adsorbent for the removal of lead ions.

    PubMed

    Mallakpour, Shadpour; Madani, Maryam

    2016-08-20

    In the current study, the surface of alpha manganese dioxide nanorod (α-MnO2) functionalized with γ-aminopropyltriethoxysilane (APTS). The α-MnO2-APTS was used as filler for preparation of chitosan (CS) nanocomposites (NCs). The α-MnO2-APTS/CS NCs were crosslinked with different amount of glutaraldehyde (GA). The effects of the GA content on the morphology, thermal properties and adsorption of NC films were studied. The Fourier transform infrared (FT-IR) results verified the grafting of APTS onto α-MnO2. The amount of APTS grafted onto α-MnO2 was found to be 20wt% by thermo gravimetric analysis. Presented results also show that with increasing crosslinker agent concentration, the thermal stability of CS films were increased. The α-MnO2-APTS/CS NCs were tested and evaluated as a potential adsorbent for the removal of lead ions. The results showed that the adsorbent exhibited a favorable performance for the removal of lead ions. Therefore, α-MnO2-APTS/CS NCs could serve as promising adsorbents. PMID:27178908

  5. 8. Detail showing concrete abutment, showing substructure of bridge, specifically ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Detail showing concrete abutment, showing substructure of bridge, specifically west side of arch and substructure. - Presumpscot Falls Bridge, Spanning Presumptscot River at Allen Avenue extension, 0.75 mile west of U.S. Interstate 95, Falmouth, Cumberland County, ME

  6. 28. MAP SHOWING LOCATION OF ARVFS FACILITY AS BUILT. SHOWS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. MAP SHOWING LOCATION OF ARVFS FACILITY AS BUILT. SHOWS LINCOLN BOULEVARD, BIG LOST RIVER, AND NAVAL REACTORS FACILITY. F.C. TORKELSON DRAWING NUMBER 842-ARVFS-101-2. DATED OCTOBER 12, 1965. INEL INDEX CODE NUMBER: 075 0101 851 151969. - Idaho National Engineering Laboratory, Advanced Reentry Vehicle Fusing System, Scoville, Butte County, ID

  7. New agents: great expectations not realized.

    PubMed

    Lancet, Jeffrey E

    2013-09-01

    A number of new agents in acute myeloid leukemia (AML) have held much promise in recent years, but most have failed to change the therapeutic landscape. Indeed, with the exception of gemtuzumab ozogamicin (which was subsequently voluntarily withdrawn from the commercial market), no new agent has been approved for acute myeloid leukemia (AML) beyond the 7 + 3 regimen, which was has been in use for over 40 years. This review touches upon the potential reasons for these failures and explores the newer therapeutic approaches being pursued in AML.

  8. Mobile Agents Applications.

    ERIC Educational Resources Information Center

    Martins, Rosane Maria; Chaves, Magali Ribeiro; Pirmez, Luci; Rust da Costa Carmo, Luiz Fernando

    2001-01-01

    Discussion of the need to filter and retrieval relevant information from the Internet focuses on the use of mobile agents, specific software components which are based on distributed artificial intelligence and integrated systems. Surveys agent technology and discusses the agent building package used to develop two applications using IBM's Aglet…

  9. Hydroxypyridonate chelating agents

    DOEpatents

    Raymond, Kenneth N.; Scarrow, Robert C.; White, David L.

    1987-01-01

    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.

  10. Promise and challenges of maternal health collaboratives.

    PubMed

    Louis, Judette M

    2015-06-01

    Quality-improvement collaboratives are just one of many tools used by health care delivery systems to address quality and safety gaps. These initiatives usually encompass specific aims, multidisciplinary teams, and information sharing. In the recent years, there has been a significant increase in the number of maternal health collaboratives with 31 states having a State Perinatal Quality Collaborative. These programs have shown promise with significant gains in the reduction of early elective deliveries. Further investments by stakeholders can help contribute the resources needed to evaluate the effectiveness and cost savings of maternal health collaboratives. PMID:25851849

  11. Aerodynamics of a promising vortex furnace design

    NASA Astrophysics Data System (ADS)

    Anufriev, I. S.; Strizhak, P. A.; Chernetskii, M. Yu.; Shadrin, E. Yu.; Sharypov, O. V.

    2015-08-01

    The aerodynamics of a promising vortex furnace design with secondary top blasting has been studied. Flow velocity fields have been measured in an isothermal laboratory model of the furnace using a digital tracer imaging (particle image velocimetry) technique. Three-dimensional diagnostics of flow structure in the combustion chamber has been carried out by the method of laser Doppler anemometry. Processing of the obtained data using the criterion of "minimum total pressure" has been used to visualize the spatial structure of the vortex core.

  12. Autophagy : Moving Benchside Promises to Patient Bedsides.

    PubMed

    Belaid, Amine; Ndiaye, Papa Diogop; Filippakis, Harilaos; Roux, Jérémie; Röttinger, Éric; Graba, Yacine; Brest, Patrick; Hofman, Paul; Mograbi, Baharia

    2015-01-01

    Survival rates of patients with metastatic or recurrent cancers have remained virtually unchanged during the past 30 years. This fact makes the need for new therapeutic options even more urgent. An attractive option would be to target autophagy, an essential quality control process that degrades toxic aggregates, damaged organelles, and signaling proteins, and acts as a tumor suppressor pathway of tumor initiation. Conversely, other fascinating observations suggest that autophagy supports cancer progression, relapse, metastasis, dormancy and resistance to therapy. This review provides an overview of the contradictory roles that autophagy plays in cancer initiation and progression and discusses the promises and challenges of current strategies that target autophagy for cancer therapy.

  13. Results of a modified PROMISE experiment

    NASA Astrophysics Data System (ADS)

    Stefani, F.; Gerbeth, G.; Gundrum, Th.; Szklarski, J.; Rüdiger, G.; Hollerbach, R.

    2008-09-01

    The PROMISE experiment relies on the fact that the critical Reynolds number for the appearance of the magnetorotational instability (MRI) in liquid metal flows drastically decreases when the purely axial magnetic field is replaced by a helical one. We report the results of a modified version of this experiments in which the radial electrical boundary conditions are changed. Special focus is laid on the role of the radial jet region where the two Ekman vortices from the top and the bottom meet each other.

  14. Autophagy : Moving Benchside Promises to Patient Bedsides.

    PubMed

    Belaid, Amine; Ndiaye, Papa Diogop; Filippakis, Harilaos; Roux, Jérémie; Röttinger, Éric; Graba, Yacine; Brest, Patrick; Hofman, Paul; Mograbi, Baharia

    2015-01-01

    Survival rates of patients with metastatic or recurrent cancers have remained virtually unchanged during the past 30 years. This fact makes the need for new therapeutic options even more urgent. An attractive option would be to target autophagy, an essential quality control process that degrades toxic aggregates, damaged organelles, and signaling proteins, and acts as a tumor suppressor pathway of tumor initiation. Conversely, other fascinating observations suggest that autophagy supports cancer progression, relapse, metastasis, dormancy and resistance to therapy. This review provides an overview of the contradictory roles that autophagy plays in cancer initiation and progression and discusses the promises and challenges of current strategies that target autophagy for cancer therapy. PMID:26452384

  15. [New agents for hypercholesterolemia].

    PubMed

    Pintó, Xavier; García Gómez, María Carmen

    2016-02-19

    An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage.

  16. Nanoparticles promise new methods to boost oncology outcomes in breast cancer.

    PubMed

    Islamian, Jalil Pirayesh; Hatamian, Milad; Rashidi, Mohammad Reza

    2015-01-01

    Different types of treatment are available for patients with breast cancer, the most being radiotherapy, chemotherapy, hormonal therapy and combination therapy. Recently, nanoparticles have been emerging as promising agents for cancer therapy and are being investigated as contrast agents, drug carriers, radiosensitizers and also for hyperthermia effects. In this review the focus is on approaches for targeted treatment of breast cancer by combining nanoparticles, chemodrugs and radiation. The availble data suggest the possibility of increased roles for combined therapy, particularly by reducing the dose of each treatment modality, and consequently minimizing related side effects.

  17. Mobile agent location in distributed environments

    NASA Astrophysics Data System (ADS)

    Fountoukis, S. G.; Argyropoulos, I. P.

    2012-12-01

    An agent is a small program acting on behalf of a user or an application which plays the role of a user. Artificial intelligence can be encapsulated in agents so that they can be capable of both behaving autonomously and showing an elementary decision ability regarding movement and some specific actions. Therefore they are often called autonomous mobile agents. In a distributed system, they can move themselves from one processing node to another through the interconnecting network infrastructure. Their purpose is to collect useful information and to carry it back to their user. Also, agents are used to start, monitor and stop processes running on the individual interconnected processing nodes of computer cluster systems. An agent has a unique id to discriminate itself from other agents and a current position. The position can be expressed as the address of the processing node which currently hosts the agent. Very often, it is necessary for a user, a processing node or another agent to know the current position of an agent in a distributed system. Several procedures and algorithms have been proposed for the purpose of position location of mobile agents. The most basic of all employs a fixed computing node, which acts as agent position repository, receiving messages from all the moving agents and keeping records of their current positions. The fixed node, responds to position queries and informs users, other nodes and other agents about the position of an agent. Herein, a model is proposed that considers pairs and triples of agents instead of single ones. A location method, which is investigated in this paper, attempts to exploit this model.

  18. Curcumin and Resveratrol as Promising Natural Remedies with Nanomedicine Approach for the Effective Treatment of Triple Negative Breast Cancer

    PubMed Central

    Shindikar, Amol; Singh, Akshita; Nobre, Malcolm; Kirolikar, Saurabh

    2016-01-01

    Researchers have made considerable progress in last few decades in understanding mechanisms underlying pathogenesis of breast cancer, its phenotypes, its molecular and genetic changes, its physiology, and its prognosis. This has allowed us to identify specific targets and design appropriate chemical entities for effective treatment of most breast cancer phenotypes, resulting in increased patient survivability. Unfortunately, these strategies have been largely ineffective in the treatment of triple negative breast cancer (TNBC). Hormonal receptors lacking render the conventional breast cancer drugs redundant, forcing scientists to identify novel targets for treatment of TNBC. Two natural compounds, curcumin and resveratrol, have been widely reported to have anticancer properties. In vitro and in vivo studies show promising results, though their effectiveness in clinical settings has been less than satisfactory, owing to their feeble pharmacokinetics. Here we discuss these naturally occurring compounds, their mechanism as anticancer agents, their shortcomings in translational research, and possible methodology to improve their pharmacokinetics/pharmacodynamics with advanced drug delivery systems. PMID:27242900

  19. Targeting advanced glycation with pharmaceutical agents: where are we now?

    PubMed

    Borg, Danielle J; Forbes, Josephine M

    2016-08-01

    Advanced glycation end products (AGEs) are the final products of the Maillard reaction, a complex process that has been studied by food chemists for a century. Over the past 30 years, the biological significance of advanced glycation has also been discovered. There is mounting evidence that advanced glycation plays a homeostatic role within the body and that food-related Maillard products, intermediates such as reactive α-dicarbonyl compounds and AGEs, may influence this process. It remains to be understood, at what point AGEs and their intermediates become pathogenic and contribute to the pathogenesis of chronic diseases that inflict current society. Diabetes and its complications have been a major focus of AGE biology due to the abundance of excess sugar and α-dicarbonyls in this family of diseases. While further temporal information is required, a number of pharmacological agents that inhibit components of the advanced glycation pathway have already showed promising results in preclinical models. These therapies appear to have a wide range of mechanistic actions to reduce AGE load. Some of these agents including Alagebrium, have translated successfully to clinical trials, while others such as aminoguanidine, have had undesirable side-effect profiles. This review will discuss different pharmacological agents that have been used to reduce AGE burden in preclinical models of disease with a focus on diabetes and its complications, compare outcomes of those therapies that have reached clinical trials, and provide further rationale for the use of inhibitors of the glycation pathway in chronic diseases. PMID:27392438

  20. Promising strategies for the prevention of dementia.

    PubMed

    Middleton, Laura E; Yaffe, Kristine

    2009-10-01

    The incidence and prevalence of dementia are expected to increase several-fold in the coming decades. Given that the current pharmaceutical treatment of dementia can only modestly improve symptoms, risk factor modification remains the cornerstone for dementia prevention. Some of the most promising strategies for the prevention of dementia include vascular risk factor control, cognitive activity, physical activity, social engagement, diet, and recognition of depression. In observational studies, vascular risk factors-including diabetes, hypertension, dyslipidemia, and obesity-are fairly consistently associated with increased risk of dementia. In addition, people with depression are at high risk for cognitive impairment. Population studies have reported that intake of antioxidants or polyunsaturated fatty acids may be associated with a reduced incidence of dementia, and it has been reported that people who are cognitively, socially, and physically active have a reduced risk of cognitive impairment. However, results from randomized trials of risk factor modification have been mixed. Most promising, interventions of cognitive and physical activity improve cognitive performance and slow cognitive decline. Future studies should continue to examine the implication of risk factor modification in controlled trials, with particular focus on whether several simultaneous interventions may have additive or multiplicative effects.

  1. The promise of microfluidic artificial lungs.

    PubMed

    Potkay, Joseph A

    2014-11-01

    Microfluidic or microchannel artificial lungs promise to enable a new class of truly portable, therapeutic artificial lungs through feature sizes and blood channel designs that closely mimic those found in their natural counterpart. These new artificial lungs could potentially: 1) have surface areas and priming volumes that are a fraction of current technologies thereby decreasing device size and reducing the foreign body response; 2) contain blood flow networks in which cells and platelets experience pressures, shear stresses, and branching angles that copy those in the human lung thereby improving biocompatibility; 3) operate efficiently with room air, eliminating the need for gas cylinders and complications associated with hyperoxemia; 4) exhibit biomimetic hydraulic resistances, enabling operation with natural pressures and eliminating the need for blood pumps; and, 5) provide increased gas exchange capacity enabling respiratory support for active patients. This manuscript reviews recent research efforts in microfluidic artificial lungs targeted at achieving the advantages above, investigates the ultimate performance and scaling limits of these devices using a proven mathematical model, and discusses the future challenges that must be overcome in order for microfluidic artificial lungs to be applied in the clinic. If all of these promising advantages are realized and the remaining challenges are met, microfluidic artificial lungs could revolutionize the field of pulmonary rehabilitation.

  2. Standard Agent Framework 1

    SciTech Connect

    Goldsmith, Steven Y.

    1999-04-06

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4) Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.

  3. Contrast agent free detection of bowel perforation using chlorophyll derivatives from food plants

    NASA Astrophysics Data System (ADS)

    Han, Jung Hyun; Jo, Young Goun; Kim, Jung Chul; Lee, Jee-Bum; Kim, Yong-Chul; Kang, Hoonsoo; Hwang, In-Wook

    2016-01-01

    Chlorophylls occur abundantly in food plants and show bright emission bands at long-wavelength regions (∼675 and ∼720 nm) compared to the autofluorescence of animal organs and peritoneal fluids. The use of these emissions as biomarkers for monitoring bowel perforation with a modality that does not involve synthetic contrast agents seems promising. To validate this, we measured the fluorescence spectra of rat organs, human peritoneal and intestinal fluids, and human intestinal fluids diluted with physiological saline. The developed technique showed a high detection sensitivity (∼50 ppm) under irrigation for abdominal surgery, highlighting the potential of this tool in the surgical setting.

  4. Promise of radiosensitizers and radioprotectors in the treatment of human cancer

    SciTech Connect

    Phillips, T.L.; Wasserman, T.H.

    1984-01-01

    Over the past 30 years, as an understanding of radiation chemistry has developed, it has been possible to develop compounds which modify the initial radiochemical event. In addition, certain physiologic means such as hyperbaric oxygen or blood flow restriction have also been developed as methods to modify radiation response through the radiochemical processes. Following the success of certain hyperbaric trials, a great effort was made to develop chemical agents which would mimic oxygen in their sensitization of hypoxic cells. A large series of compounds have now been identified with such properties and several of these have entered clinical trial. The first compound to receive widespread testing, misonidazole, has proven too toxic to be used in adequate doses for clinically relevant sensitization. Two new nitroimidazole analogs, which are excluded from the central nervous system, promise to allow much higher degrees of sensitization in planned clinical trials and new non-nitro drugs are under development. Radioprotection can be achieved through various methods, including restriction in blood flow and the use of sulfhydryl-containing compounds which again modify the initial radiochemical events. To be successful in tumor therapy, such agents must be selective in protecting the normal tissues. One class of compounds, the thiophosphates, show differential protection of normal tissue vis-a-vis tumor through several mechanisms. After extensive animal testing, one of these compounds, WR 2721, is now in phase I clinical testing, with phase II evaluation planned for the near future. Other potential sensitizers with varying degrees of differential activity in tumor versus normal tissue are also discussed.

  5. What Do Blood Tests Show?

    MedlinePlus

    ... shows the ranges for blood glucose levels after 8 to 12 hours of fasting (not eating). It shows the normal range and the abnormal ranges that are a sign of prediabetes or diabetes. Plasma Glucose Results (mg/dL)* Diagnosis 70 to 99 ...

  6. Sustainable Society Formed by Unselfish Agents

    NASA Astrophysics Data System (ADS)

    Kikuchi, Toshiko

    It has been pointed out that if the social configuration of the three relations (market, communal and obligatory relations) is not balanced, a market based society as a total system fails. Using multi-agent simulations, this paper shows that a sustainable society is formed when all three relations are integrated and function respectively. When agent trades are based on the market mechanism (i.e., agents act in their own interest and thus only market relations exist), weak agents who cannot perform transactions die. If a compulsory tax is imposed to enable all weak agents to survive (i.e., obligatory relations exist), then the fiscal deficit increases. On the other hand, if agents who have excess income undertake the unselfish action of distributing their surplus to the weak agents (i.e., communal relations exist), then trade volume increases. It is shown that the existence of unselfish agents is necessary for the realization of a sustainable society. However, the survival of all agents is difficult in a communal society. In an artificial society, for all agents survive and fiscal balance to be maintained, all three social relations need to be fully integrated. These results show that adjusting the balance of the three social relations well lead to the realization of a sustainable society.

  7. Satellite Movie Shows Erika Dissipate

    NASA Video Gallery

    This animation of visible and infrared imagery from NOAA's GOES-West satellite from Aug. 27 to 29 shows Tropical Storm Erika move through the Eastern Caribbean Sea and dissipate near eastern Cuba. ...

  8. 47 CFR 74.131 - Licensing requirements, necessary showing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Licensing requirements, necessary showing. 74... Experimental Broadcast Stations § 74.131 Licensing requirements, necessary showing. (a) An applicant for a new... research and experimentation in the technical phases of broadcasting which indicates reasonable promise...

  9. A promising new thermoelectric material - Ruthenium silicide

    NASA Technical Reports Server (NTRS)

    Vining, Cronin B.; Mccormack, Joseph A.; Zoltan, Andrew; Zoltan, Leslie D.

    1991-01-01

    Experimental and theoretical efforts directed toward increasing thermoelectric figure of merit values by a factor of 2 or 3 have been encouraging in several respects. An accurate and detailed theoretical model developed for n-type silicon-germanium (SiGe) indicates that ZT values several times higher than currently available are expected under certain conditions. These new, high ZT materials are expected to be significantly different from SiGe, but not unreasonably so. Several promising candidate materials have been identified which may meet the conditions required by theory. One such candidate, ruthenium silicide, currently under development at JPL, has been estimated to have the potential to exhibit figure of merit values 4 times higher than conventional SiGe materials. Recent results are summarized.

  10. Promising Candidates for Prevention of Allergy

    PubMed Central

    Gern, James E.

    2015-01-01

    Recent advances in understanding environmental risk factors for allergic diseases in children has led to renewed efforts aimed at prevention. Factors that modify the probability of developing allergies include prenatal exposures, mode of delivery, diet, patterns of medication use, and exposure to pets and farm animals. Recent advances in microbial detection techniques demonstrate that exposure to diverse microbial communities in early life is associated with a reduction in allergic disease. In fact, microbes and their metabolic products may be essential for normal immune development. Identification of these risk factors has provided new targets for prevention of allergic diseases, and possibilities of altering microbial exposure and colonization to reduce the incidence of allergies is a promising approach. This review examines the rationale, feasibility and potential impact for the prevention of childhood allergic diseases, and explores possible strategies for enhancing exposure to beneficial microbes. PMID:26145984

  11. Autism: Pathophysiology and Promising Herbal Remedies.

    PubMed

    Bahmani, Mahmoud; Sarrafchi, Amir; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud

    2016-01-01

    Autism is a comprehensive growth abnormality in which social skills, language, communication, and behavioral skills are developed with delay and as diversionary. The reasons for autism are unclear, but various theories of genetics, immunity, biological, and psychosocial factors have been proffered. In fact, autism is a complex disorder with distinct causes that usually co-occur. Although no medicine has been recognized to treat this disorder, pharmacological treatments can be effective in reducing its signs, such as self-mutilation, aggression, repetitive and stereotyped behaviors, inattention, hyperactivity, and sleeping disorders. Recently, complementary and alternative approaches have been considered to treat autism. Ginkgo biloba is one of the most effective plants with an old history of applications in neuropsychological disorders which recently is used for autism. The present review discusses the recent findings, pathophysiology, and etiology of autism and thereafter addresses the promising results of herbal remedies.

  12. Earthquake prediction; new studies yield promising results

    USGS Publications Warehouse

    Robinson, R.

    1974-01-01

    On Agust 3, 1973, a small earthquake (magnitude 2.5) occurred near Blue Mountain Lake in the Adirondack region of northern New York State. This seemingly unimportant event was of great significance, however, because it was predicted. Seismologsits at the Lamont-Doherty geologcal Observatory of Columbia University accurately foretold the time, place, and magnitude of the event. Their prediction was based on certain pre-earthquake processes that are best explained by a hypothesis known as "dilatancy," a concept that has injected new life and direction into the science of earthquake prediction. Although much mroe reserach must be accomplished before we can expect to predict potentially damaging earthquakes with any degree of consistency, results such as this indicate that we are on a promising road. 

  13. The promise and paradox of cultural competence.

    PubMed

    Hester, Rebecca J

    2012-12-01

    Cultural competence has become a ubiquitous and unquestioned aspect of professional formation in medicine. It has been linked to efforts to eliminate race-based health disparities and to train more compassionate and sensitive providers. In this article, I question whether the field of cultural competence lives up to its promise. I argue that it does not because it fails to grapple with the ways that race and racism work in U.S. society today. Unless we change our theoretical apparatus for dealing with diversity to one that more critically engages with the complexities of race, I suggest that unequal treatment and entrenched health disparities will remain. If the field of cultural competence incorporates the lessons of critical race scholarship, however, it would not only need to transform its theoretical foundation, it would also need to change its name.

  14. The promising trajectory of autism therapeutics discovery.

    PubMed

    Silverman, Jill L; Crawley, Jacqueline N

    2014-07-01

    Pharmacological interventions for neurodevelopmental disorders are increasingly tractable. Autism is a neurodevelopmental disorder that affects approximately 1% of the population. Currently, the standard of care is early behavioral therapy. No approved medical treatments for the diagnostic symptoms are available. Strong evidence for genetic causes of autism implicates proteins that mediate synaptic transmission and structure. Mouse models with targeted mutations in these synaptic genes display behavioral symptoms relevant to the social communication abnormalities and repetitive behaviors that define autism spectrum disorder (ASD), along with biological abnormalities in synaptic physiology and morphology. As we discuss here, promising pharmacological targets, emerging from the mouse model studies, are now being pursued in early clinical trials. Thus, a high-prevalence disorder that was previously considered to be medically untreatable is now moving into the therapeutic arena.

  15. Review of Some Promising Fractional Physical Models

    NASA Astrophysics Data System (ADS)

    Tarasov, Vasily E.

    2013-04-01

    Fractional dynamics is a field of study in physics and mechanics investigating the behavior of objects and systems that are characterized by power-law nonlocality, power-law long-term memory or fractal properties by using integrations and differentiation of non-integer orders, i.e., by methods in the fractional calculus. This paper is a review of physical models that look very promising for future development of fractional dynamics. We suggest a short introduction to fractional calculus as a theory of integration and differentiation of noninteger order. Some applications of integro-differentiations of fractional orders in physics are discussed. Models of discrete systems with memory, lattice with long-range inter-particle interaction, dynamics of fractal media are presented. Quantum analogs of fractional derivatives and model of open nano-system systems with memory are also discussed.

  16. The promise and peril of healthcare forecasting.

    PubMed

    Wharam, J Frank; Weiner, Jonathan P

    2012-03-01

    Health plans and physician groups increasingly use sophisticated tools to predict individual patient outcomes. Such analytics will accelerate as US medicine enters the digital age. Promising applications of forecasting include better targeting of disease management as well as innovative patient care approaches such as personalized health insurance and clinical decision support systems. In addition, stakeholders will use predictions to advance their organizational agendas, and unintended consequences could arise. Forecasting-based interventions might have uncertain effectiveness, focus on cost savings rather than long-term health, or specifically exclude disadvantaged populations. Policy makers, health plans, and method developers should adopt strategies that address these concerns in order to maximize the benefit of healthcare forecasting on the long-term health of patients.

  17. The promise of Lean in health care.

    PubMed

    Toussaint, John S; Berry, Leonard L

    2013-01-01

    An urgent need in American health care is improving quality and efficiency while controlling costs. One promising management approach implemented by some leading health care institutions is Lean, a quality improvement philosophy and set of principles originated by the Toyota Motor Company. Health care cases reveal that Lean is as applicable in complex knowledge work as it is in assembly-line manufacturing. When well executed, Lean transforms how an organization works and creates an insatiable quest for improvement. In this article, we define Lean and present 6 principles that constitute the essential dynamic of Lean management: attitude of continuous improvement, value creation, unity of purpose, respect for front-line workers, visual tracking, and flexible regimentation. Health care case studies illustrate each principle. The goal of this article is to provide a template for health care leaders to use in considering the implementation of the Lean management system or in assessing the current state of implementation in their organizations. PMID:23274021

  18. The Challenge and Promise of Glycomics

    PubMed Central

    Cummings, Richard D.; Pierce, J. Michael

    2014-01-01

    Glycomics is a broad and emerging scientific discipline focused on defining the structures and functional roles of glycans in biological systems. The staggering complexity of the glycome, minimally defined as the repertoire of glycans expressed in a cell or organism, has resulted in many challenges that must be overcome; these are being addressed by new advances in mass spectrometry, as well as expansion of genetic and cell biology studies. Conversely, identifying the specific glycan recognition determinants of glycan-binding proteins by employing the new technology of glycan microarrays is providing insights into how glycans function in recognition and signaling within an organism and with microbes and pathogens. The promises of a more complete knowledge of glycomes are immense in that glycan modifications of intracellular and extracellular proteins have critical functions in almost all biological pathways. PMID:24439204

  19. Nanomedicine delivers promising treatments for rheumatoid arthritis

    PubMed Central

    Prasad, Leena Kumari; O’Mary, Hannah; Cui, Zhengrong

    2015-01-01

    An increased understanding in the pathophysiology of chronic inflammatory diseases, such as rheumatoid arthritis, reveals that the diseased tissue and the increased presence of macrophages and other overexpressed molecules within the tissue can be exploited to enhance the delivery of nanomedicine. Nanomedicine can passively accumulate into chronic inflammatory tissues via the enhanced permeability and retention phenomenon, or be surface conjugated with a ligand to actively bind to receptors overexpressed by cells within chronic inflammatory tissues, leading to increased efficacy and reduced systemic side-effects. This review highlights the research conducted over the past decade on using nanomedicine for potential treatment of rheumatoid arthritis and summarizes some of the major findings and promising opportunities on using nanomedicine to treat this prevalent and chronic disease. PMID:26084368

  20. Cyclooxygenase-2 inhibitors: promise or peril?

    PubMed Central

    Mengle-Gaw, Laurel J; Schwartz, Benjamin D

    2002-01-01

    The discovery of two isoforms of the cyclooxygenase enzyme, COX-1 and COX-2, and the development of COX-2-specific inhibitors as anti-inflammatories and analgesics have offered great promise that the therapeutic benefits of NSAIDs could be optimized through inhibition of COX-2, while minimizing their adverse side effect profile associated with inhibition of COX-1. While COX-2 specific inhibitors have proven to be efficacious in a variety of inflammatory conditions, exposure of large numbers of patients to these drugs in postmarketing studies have uncovered potential safety concerns that raise questions about the benefit/risk ratio of COX-2-specific NSAIDs compared to conventional NSAIDs. This article reviews the efficacy and safety profiles of COX-2-specific inhibitors, comparing them with conventional NSDAIDs. PMID:12467519

  1. The promise of Lean in health care.

    PubMed

    Toussaint, John S; Berry, Leonard L

    2013-01-01

    An urgent need in American health care is improving quality and efficiency while controlling costs. One promising management approach implemented by some leading health care institutions is Lean, a quality improvement philosophy and set of principles originated by the Toyota Motor Company. Health care cases reveal that Lean is as applicable in complex knowledge work as it is in assembly-line manufacturing. When well executed, Lean transforms how an organization works and creates an insatiable quest for improvement. In this article, we define Lean and present 6 principles that constitute the essential dynamic of Lean management: attitude of continuous improvement, value creation, unity of purpose, respect for front-line workers, visual tracking, and flexible regimentation. Health care case studies illustrate each principle. The goal of this article is to provide a template for health care leaders to use in considering the implementation of the Lean management system or in assessing the current state of implementation in their organizations.

  2. Discovery of 3,3'-diindolylmethanes as potent antileishmanial agents.

    PubMed

    Bharate, Sandip B; Bharate, Jaideep B; Khan, Shabana I; Tekwani, Babu L; Jacob, Melissa R; Mudududdla, Ramesh; Yadav, Rammohan R; Singh, Baljinder; Sharma, P R; Maity, Sudip; Singh, Baldev; Khan, Ikhlas A; Vishwakarma, Ram A

    2013-05-01

    An efficient protocol for synthesis of 3,3'-diindolylmethanes using recyclable Fe-pillared interlayered clay (Fe-PILC) catalyst under aqueous medium has been developed. All synthesized 3,3'-diindolylmethanes showed promising antileishmanial activity against Leishmania donovani promastigotes as well as axenic amastigotes. Structure-activity relationship analysis revealed that nitroaryl substituted diindolylmethanes showed potent antileishmanial activity. The 4-nitrophenyl linked 3,3'-diindolylmethane 8g was found to be the most potent antileishmanial analog showing IC50 values of 7.88 and 8.37 μM against both L. donovani promastigotes and amastigotes, respectively. Further, a pharmacophore based QSAR model was established to understand the crucial molecular features of 3,3'-diindolylmethanes essential for potent antileishmanial activity. These compounds also exhibited promising antifungal activity against Cryptococcus neoformans, wherein fluorophenyl substituted 3,3'-diindolylmethanes were found to be most potent antifungal agents. Developed synthetic protocol will be useful for economical and eco-friendly synthesis of potent antileishmanial and antifungal 3,3'-diindolylmethane class of compounds. PMID:23517732

  3. Promising avenues of therapeutics for bipolar illness

    PubMed Central

    Post, Robert M.

    2008-01-01

    Basic scientific advances in understanding the neuropsychobioloqy of bipolar disorder have given us a multitude of opportunities to explore and exploit new avenues of therapeutics. Pharmacotherapeutic approaches include: neuropeptides (agonists such as thyrotropin-releasing hormone and antagonists such as corticotropin-releasing hormone), neurotrophic factors (especially brain-derived neurotrophic factor), and glutamatergic mechanisms (such as riluzole, ketamine, and antagonists of the NR-2B subunit of the glutamate receptor). Physiological interventions that would offer alternatives to electroconvulsive therapy include: repeated transcranial magnetic stimulation, especially at more intense stimulation parameters; magnetic stimulation therapy (seizures induced more focally by magnetic rather than electrical stimulation with resulting reduced meaning loss); vagal nerve stimulation, and deep brain stimulation. However, these, as well as the panoply of existing treatments, require further intensive investigation to place each of them in the proper therapeutic seguence and combination for the individual patient, based on development of better clinical and biological predictors of response. Large clinical trial networks and development of systematic research in clinical practice settings, such as that featured by the National Cancer institute for cancer chemotherapy, would greatly accelerate the progress in incorporating new, as well as existing, agents into the best treatment strategies. The bipolar disorders, which are increasingly recognized as complex, highly comorbid conditions with a high morbidity and mortality, of which the majority start in childhood and adolescence, are not likely to respond completely to any single new treatment agent, and new public health initiatives and research strategies are needed as much as any new single treatment advance. PMID:18689289

  4. Promising avenues of therapeutics for bipolar illness.

    PubMed

    Post, Robert M

    2008-01-01

    Basic scientific advances in understanding the neuropsychobiology of bipolar disorder have given us a multitude of opportunities to explore and exploit new avenues of therapeutics. Pharmacotherapeutic approaches include: neuropeptides (agonists such as thyrotropin-releasing hormone and antagonists such as corticotropin-releasing hormone), neurotrophic factors (especially brain-derived neurotrophic factor), and glutamatergic mechanisms (such as riluzole, ketamine, and antagonists of the NR-2B subunit of the glutamate receptor). Physiological interventions that would offer alternatives to electroconvulsive therapy include: repeated transcranial magnetic stimulation, especially at more intense stimulation parameters; magnetic stimulation therapy (seizures induced more focally by magnetic rather than electrical stimulation with resulting reduced meaning loss); vagal nerve stimulation, and deep brain stimulation. However, these, as well as the panoply of existing treatments, require further intensive investigation to place each of them in the proper therapeutic sequence and combination for the individual patient, based on development of better clinical and biological predictors of response. Large clinical trial networks and development of systematic research in clinical practice settings, such as that featured by the National Cancer Institute for cancer chemotherapy, would greatly accelerate the progress in incorporating new, as well as existing, agents into the best treatment strategies. The bipolar disorders, which are increasingly recognized as complex, highly comorbid conditions with a high morbidity and mortality, of which the majority start in childhood and adolescence, are not likely to respond completely to any single new treatment agent, and new public health initiatives and research strategies are needed as much as any new single treatment advance.

  5. Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer

    PubMed Central

    Feng, Juntao; Gou, Jinhai; Jia, Jia; Yi, Tao; Cui, Tao; Li, Zhengyu

    2016-01-01

    Yes-associated protein (YAP) is a key transcriptional coactivator of Hippo pathway and has been shown to be an oncoprotein in ovarian cancer (OC). Verteporfin (VP), clinically used in photodynamic therapy for neovascular macular degeneration, has been recently proven to be a suppressor of YAP–TEAD complex and has shown potential in anticancer treatment. In this study, we aimed to explore the potential effect of VP in the treatment of OC. Our results showed that VP led to inhibition of proliferation in a time- and dose-dependent manner and to the suppression of migratory and invasive capacities of OC cells. Western blot and real-time polymerase chain reaction demonstrated that VP induced YAP cytoplasmic retention and deregulated inducible YAP and CCNs in OC cells. In vivo, VP exerted a significant effect on tumor growth in OVCAR8 xenograft mice, resulting in tumor nodules with lower average weight and reduced volume of gross ascites. In addition, VP treatment remarkably upregulated cytoplasmic YAP and phosphorylation YAP and downregulated CCN1 and CCN2, but exerted little effect on YAP-upstream components in Hippo pathway. In conclusion, our results suggested that VP may be a promising agent for OC, acting by suppressing YAP–TEAD complex.

  6. Verteporfin, a suppressor of YAP-TEAD complex, presents promising antitumor properties on ovarian cancer.

    PubMed

    Feng, Juntao; Gou, Jinhai; Jia, Jia; Yi, Tao; Cui, Tao; Li, Zhengyu

    2016-01-01

    Yes-associated protein (YAP) is a key transcriptional coactivator of Hippo pathway and has been shown to be an oncoprotein in ovarian cancer (OC). Verteporfin (VP), clinically used in photodynamic therapy for neovascular macular degeneration, has been recently proven to be a suppressor of YAP-TEAD complex and has shown potential in anticancer treatment. In this study, we aimed to explore the potential effect of VP in the treatment of OC. Our results showed that VP led to inhibition of proliferation in a time- and dose-dependent manner and to the suppression of migratory and invasive capacities of OC cells. Western blot and real-time polymerase chain reaction demonstrated that VP induced YAP cytoplasmic retention and deregulated inducible YAP and CCNs in OC cells. In vivo, VP exerted a significant effect on tumor growth in OVCAR8 xenograft mice, resulting in tumor nodules with lower average weight and reduced volume of gross ascites. In addition, VP treatment remarkably upregulated cytoplasmic YAP and phosphorylation YAP and downregulated CCN1 and CCN2, but exerted little effect on YAP-upstream components in Hippo pathway. In conclusion, our results suggested that VP may be a promising agent for OC, acting by suppressing YAP-TEAD complex. PMID:27621651

  7. Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer

    PubMed Central

    Feng, Juntao; Gou, Jinhai; Jia, Jia; Yi, Tao; Cui, Tao; Li, Zhengyu

    2016-01-01

    Yes-associated protein (YAP) is a key transcriptional coactivator of Hippo pathway and has been shown to be an oncoprotein in ovarian cancer (OC). Verteporfin (VP), clinically used in photodynamic therapy for neovascular macular degeneration, has been recently proven to be a suppressor of YAP–TEAD complex and has shown potential in anticancer treatment. In this study, we aimed to explore the potential effect of VP in the treatment of OC. Our results showed that VP led to inhibition of proliferation in a time- and dose-dependent manner and to the suppression of migratory and invasive capacities of OC cells. Western blot and real-time polymerase chain reaction demonstrated that VP induced YAP cytoplasmic retention and deregulated inducible YAP and CCNs in OC cells. In vivo, VP exerted a significant effect on tumor growth in OVCAR8 xenograft mice, resulting in tumor nodules with lower average weight and reduced volume of gross ascites. In addition, VP treatment remarkably upregulated cytoplasmic YAP and phosphorylation YAP and downregulated CCN1 and CCN2, but exerted little effect on YAP-upstream components in Hippo pathway. In conclusion, our results suggested that VP may be a promising agent for OC, acting by suppressing YAP–TEAD complex. PMID:27621651

  8. National Orange Show Photovoltaic Demonstration

    SciTech Connect

    Dan Jimenez Sheri Raborn, CPA; Tom Baker

    2008-03-31

    National Orange Show Photovoltaic Demonstration created a 400KW Photovoltaic self-generation plant at the National Orange Show Events Center (NOS). The NOS owns a 120-acre state fairground where it operates an events center and produces an annual citrus fair known as the Orange Show. The NOS governing board wanted to employ cost-saving programs for annual energy expenses. It is hoped the Photovoltaic program will result in overall savings for the NOS, help reduce the State's energy demands as relating to electrical power consumption, improve quality of life within the affected grid area as well as increase the energy efficiency of buildings at our venue. In addition, the potential to reduce operational expenses would have a tremendous effect on the ability of the NOS to service its community.

  9. "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

  10. Arches showing UV flaring activity

    NASA Technical Reports Server (NTRS)

    Fontenla, J. M.

    1988-01-01

    The UVSP data obtained in the previous maximum activity cycle show the frequent appearance of flaring events in the UV. In many cases these flaring events are characterized by at least two footpoints which show compact impulsive non-simultaneous brightenings and a fainter but clearly observed arch developes between the footpoints. These arches and footpoints are observed in line corresponding to different temperatures, as Lyman alpha, N V, and C IV, and when observed above the limb display large Doppler shifts at some stages. The size of the arches can be larger than 20 arcsec.

  11. The Grape Antioxidant Resveratrol for Skin Disorders: Promise, Prospects, and Challenges

    PubMed Central

    Ndiaye, Mary; Philippe, Carol; Mukhtar, Hasan; Ahmad, Nihal

    2011-01-01

    Resveratrol, a phytoalexin antioxidant found in red grapes, has been shown to have both chemopreventive and therapeutic effects against many diseases and disorders, including those of the skin. Studies have shown protective effects of resveratrol against ultraviolet radiation mediated oxidative stress and cutaneous damages including skin cancer. Because many of the skin conditions stem from ultraviolet radiation and oxidative stress, this antioxidant appears to have promise and prospects against a wide range of cutaneous disorders including skin aging and skin cancers. However, there are a few roadblocks in the way of this promising agent regarding its translation from the bench to the bedside. This review discusses the promise and prospects of resveratrol in the management of skin disorders and the associated challenges. PMID:21215251

  12. Muscle wasting in disease: molecular mechanisms and promising therapies.

    PubMed

    Cohen, Shenhav; Nathan, James A; Goldberg, Alfred L

    2015-01-01

    Atrophy occurs in specific muscles with inactivity (for example, during plaster cast immobilization) or denervation (for example, in patients with spinal cord injuries). Muscle wasting occurs systemically in older people (a condition known as sarcopenia); as a physiological response to fasting or malnutrition; and in many diseases, including chronic obstructive pulmonary disorder, cancer-associated cachexia, diabetes, renal failure, cardiac failure, Cushing syndrome, sepsis, burns and trauma. The rapid loss of muscle mass and strength primarily results from excessive protein breakdown, which is often accompanied by reduced protein synthesis. This loss of muscle function can lead to reduced quality of life, increased morbidity and mortality. Exercise is the only accepted approach to prevent or slow atrophy. However, several promising therapeutic agents are in development, and major advances in our understanding of the cellular mechanisms that regulate the protein balance in muscle include the identification of several cytokines, particularly myostatin, and a common transcriptional programme that promotes muscle wasting. Here, we discuss these new insights and the rationally designed therapies that are emerging to combat muscle wasting.

  13. Volatile aldehydes are promising broad-spectrum postharvest insecticides.

    PubMed

    Hammond, D G; Rangel, S; Kubo, I

    2000-09-01

    A variety of naturally occurring aldehydes common in plants have been evaluated for their insecticidal activity and for phytotoxicity to postharvest fruits, vegetables, and grains. Twenty-nine compounds were initially screened for their activity against aphids on fava bean leaf disks. Application under reduced pressure (partial vacuum) for the first quarter of fumigation increased insecticidal activity severalfold. The 11 best aldehydes were assayed against aphids placed under the third leaf of whole heads of iceberg lettuce using the same two-tier reduced-pressure regime, which caused no additional detriment to the commodity over fumigation at atmospheric pressure. Phytotoxicity to naked and wrapped iceburg lettuce, green and red table grapes, lemon, grapefruit, orange, broccoli, avocado, cabbage, pinto bean, and rice at doses that killed 100% of aphids was recorded for three promising fumigants: propanal, (E)-2-pentenal, and 2-methyl-(E)-2-butenal. These three compounds have excellent potential as affordable postharvest insect control agents, killing 100% of the aphids with little or no detectable harm to a majority of the commodities tested. Preliminary assays indicate that similar doses are also effective against mealybugs, thrips, and whitefly. PMID:10995371

  14. Microencapsulation: A promising technique for controlled drug delivery

    PubMed Central

    Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.

    2010-01-01

    Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed. PMID:21589795

  15. Trust and cooperation among economic agents

    PubMed Central

    Dasgupta, Partha

    2009-01-01

    The units that are subject to selection pressure in evolutionary biology are ‘strategies’, which are conditional actions (‘Do P if X occurs, otherwise do Q’). In contrast, the units in economics select strategies from available menus so as to further their projects and purposes. As economic agents do not live in isolation, each agent's optimum choice, in general, depends on the choices made by others. Because their projects and purposes involve the future, not just the present, each agent reasons about the likely present and future consequences of their respective choices. That is why beliefs, about what others may do and what the consequences of those choices could be, are at the basis of strategy selection. A catalogue of social environments is constructed in which agents not only promise each other's cooperation, but also rationally believe that the promises will be kept. Unfortunately, non-cooperation arising from mistrust can be the outcome in those same environments: societies harbour multiple ‘equilibria’ and can skid from cooperation to non-cooperation. Moreover, a pre-occupation among analysts with the Prisoners' Dilemma game has obscured the fact that cooperative arrangements can harbour not only inequality, but also exploitation. The analysis is used to discuss why international cooperation over the use of global public goods has proved to be so elusive. PMID:19805436

  16. Trust and cooperation among economic agents.

    PubMed

    Dasgupta, Partha

    2009-11-12

    The units that are subject to selection pressure in evolutionary biology are 'strategies', which are conditional actions ('Do P if X occurs, otherwise do Q'). In contrast, the units in economics select strategies from available menus so as to further their projects and purposes. As economic agents do not live in isolation, each agent's optimum choice, in general, depends on the choices made by others. Because their projects and purposes involve the future, not just the present, each agent reasons about the likely present and future consequences of their respective choices. That is why beliefs, about what others may do and what the consequences of those choices could be, are at the basis of strategy selection. A catalogue of social environments is constructed in which agents not only promise each other's cooperation, but also rationally believe that the promises will be kept. Unfortunately, non-cooperation arising from mistrust can be the outcome in those same environments: societies harbour multiple 'equilibria' and can skid from cooperation to non-cooperation. Moreover, a pre-occupation among analysts with the Prisoners' Dilemma game has obscured the fact that cooperative arrangements can harbour not only inequality, but also exploitation. The analysis is used to discuss why international cooperation over the use of global public goods has proved to be so elusive. PMID:19805436

  17. Create a Polarized Light Show.

    ERIC Educational Resources Information Center

    Conrad, William H.

    1992-01-01

    Presents a lesson that introduces students to polarized light using a problem-solving approach. After illustrating the concept using a slinky and poster board with a vertical slot, students solve the problem of creating a polarized light show using Polya's problem-solving methods. (MDH)

  18. The promise of air cargo: System aspects and vehicle design

    NASA Technical Reports Server (NTRS)

    Whitehead, A. H., Jr.

    1976-01-01

    The current operation of the air cargo system is reviewed. An assessment of the future of air cargo is provided by: (1) analyzing statistics and trends, (2) by noting system problems and inefficiencies, (3) by analyzing characteristics of 'air eligible' commodities, and (4) by showing the promise of new technology for future cargo aircraft with significant improvements in costs and efficiency. The following topics are discussed: (1) air cargo demand forecasts; (2) economics of air cargo transport; (3) the integrated air cargo system; (4) evolution of airfreighter design; and (5) the span distributed load concept.

  19. Investigation of new superhard carbon allotropes with promising electronic properties

    SciTech Connect

    Kvashnina, Yulia A.; Kvashnin, Alexander G.; Sorokin, Pavel B.

    2013-11-14

    During the systematic search for a new superhard carbon allotrope, we predicted three structures with promising physical properties. Our electronic structure calculations show that these materials have a semiconducting band gap and a high carrier mobility comparable with diamond. The simulated x-ray diffraction patterns of the proposed materials are in a good agreement with the experimental X-ray spectra. Evaluated phase transition pressures from graphite to the new proposed carbon phases are smaller than 25 GPa and close to the experimental values.

  20. Evolutionary algorithms and multi-agent systems

    NASA Astrophysics Data System (ADS)

    Oh, Jae C.

    2006-05-01

    This paper discusses how evolutionary algorithms are related to multi-agent systems and the possibility of military applications using the two disciplines. In particular, we present a game theoretic model for multi-agent resource distribution and allocation where agents in the environment must help each other to survive. Each agent maintains a set of variables representing actual friendship and perceived friendship. The model directly addresses problems in reputation management schemes in multi-agent systems and Peer-to-Peer distributed systems. We present algorithms based on evolutionary game process for maintaining the friendship values as well as a utility equation used in each agent's decision making. For an application problem, we adapted our formal model to the military coalition support problem in peace-keeping missions. Simulation results show that efficient resource allocation and sharing with minimum communication cost is achieved without centralized control.

  1. A New Understanding of Chemical Agent Release

    SciTech Connect

    Nakafuji, G; Greenman, R; Theofanous, T

    2002-07-24

    The evolution of thickened chemical agent released at supersonic velocities, due to a missile defense intercept or a properly functioning warhead, has been misunderstood. Current and historical experimental and modeling efforts have attributed agent breakup to a variety of droplet breakup mechanisms. According to this model, drops of agent fragment into subsequent generations of smaller drops until a stable drop size is reached. Recent experimental data conducted in a supersonic wind tunnel show that agent breakup is not driven by any droplet breakup mechanism. The breakup of agent is instead governed by viscoelastic behavior and aerodynamic history effects. This viscoelastic breakup mechanism results in the formation of threads and sheets of liquid, instead of drops. The evolution and final state of agent released has broad implications not only for aerobreakup models, but also for all atmospheric dispersion models.

  2. Promise Neighborhoods: The Promise and Politics of Community Capacity Building as Urban School Reform

    ERIC Educational Resources Information Center

    Horsford, Sonya Douglass; Sampson, Carrie

    2014-01-01

    The purpose of this inquiry is to consider how the U.S. Department of Education's Promise Neighborhoods (PNs) program can improve persistently low-achieving urban schools by making their "neighborhoods whole again" through community capacity building for education reform. As the "first federal initiative to put education at the…

  3. Fulfilling The Pittsburgh Promise[R]: Early Progress of Pittsburgh's Postsecondary Scholarship Program. Monograph

    ERIC Educational Resources Information Center

    Gonzalez, Gabriella C.; Bozick, Robert; Tharp-Taylor, Shannah; Phillips, Andrea

    2011-01-01

    This report presents a detailed assessment of the extent to which "The Pittsburgh Promise"--a postsecondary education scholarship intended to remedy the area's population decline, foster high school completion and college readiness among Pittsburgh district students, and prepare a capable and energetic workforce for the city--has met its goals to…

  4. Bringing Promise to Washington, DC. The DC Promise Neighborhood Initiative. Program on Neighborhoods and Youth Development

    ERIC Educational Resources Information Center

    Comey, Jennifer; Scott, Molly M.; Popkin, Susan J.; Falkenburger, Elsa

    2012-01-01

    The U.S. Department of Education's Promise Neighborhood Initiative (DCPNI) is one of the Obama administration's major antipoverty initiatives and a core strategy of the White House's Neighborhood Revitalization Initiative. It is intended to improve educational outcomes by creating a continuum of school readiness, academic services, and family and…

  5. Magic Carpet Shows Its Colors

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The upper left image in this display is from the panoramic camera on the Mars Exploration Rover Spirit, showing the 'Magic Carpet' region near the rover at Gusev Crater, Mars, on Sol 7, the seventh martian day of its journey (Jan. 10, 2004). The lower image, also from the panoramic camera, is a monochrome (single filter) image of a rock in the 'Magic Carpet' area. Note that colored portions of the rock correlate with extracted spectra shown in the plot to the side. Four different types of materials are shown: the rock itself, the soil in front of the rock, some brighter soil on top of the rock, and some dust that has collected in small recesses on the rock face ('spots'). Each color on the spectra matches a line on the graph, showing how the panoramic camera's different colored filters are used to broadly assess the varying mineral compositions of martian rocks and soils.

  6. Discovery of new anticancer agents from higher plants

    PubMed Central

    Pan, Li; Chai, Hee-Byung; Kinghorn, A. Douglas

    2012-01-01

    1. ABSTRACT Small organic molecules derived from higher plants have been one of the mainstays of cancer chemotherapy for approximately the past half a century. In the present review, selected single chemical entity natural products of plant origin and their semi-synthetic derivatives currently in clinical trials are featured as examples of new cancer chemotherapeutic drug candidates. Several more recently isolated compounds obtained from plants showing promising in vivo biological activity are also discussed in terms of their potential as anticancer agents, with many of these obtained from species that grow in tropical regions. Since extracts of only a relatively small proportion of the ca. 300,000 higher plants on earth have been screened biologically to date, bioactive compounds from plants should play an important role in future anticancer drug discovery efforts. PMID:22202049

  7. Chemopreventive agents targeting tumor microenvironment.

    PubMed

    Sharma, Sharada H; Thulasingam, Senthilkumar; Nagarajan, Sangeetha

    2016-01-15

    Recent studies have shown that tumor development and progression depend not only on the perturbed genes that govern cell proliferation, but is also highly determined by the non-tumor cells of the stromal compartment surrounding the tumor called tumor microenvironment (TME). These findings highlight the importance of targeting the microenvironment in combination with therapies aimed at tumor cells as a valuable approach. The innate and adaptive immune cells in the TME interact among themselves and also with the endothelial cells, pericytes and mast cells of the stromal compartment through various autocrine and paracrine manner to regulate abnormal cell proliferation. Direct cytotoxic killing of cancer cells and/or reversion of the immunosuppressive TME are to be considered as better strategies for chemoprevention and chemotherapy. With a growing emphasis on a "hallmark targeting" strategy for cancer therapy, the TME now appears as a promising target for cancer prevention using natural products. Clarification on the nontumor stromal cells, the mediators involved, interactions with immune response cells, and immune-evasive mechanisms are needed in order to manipulate the characteristics of the TME by natural pharmacological agents to design effective therapies. This review will provide a glimpse on the roles played by various non-tumor cells in tumor progression and their intervention by pharmacological agents. PMID:26679106

  8. Nanoparticle-based theranostic agents

    PubMed Central

    Xie, Jin; Lee, Seulki; Chen, Xiaoyuan

    2010-01-01

    Theranostic nanomedicine is emerging as a promising therapeutic paradigm. It takes advantage of the high capacity of nanoplatforms to ferry cargo and loads onto them both imaging and therapeutic functions. The resulting nanosystems, capable of diagnosis, drug delivery and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine, and much research effort has been devoted toward that goal. A convenience in constructing such function-integrated agents is that many nanoplatforms are already, themselves, imaging agents. Their well developed surface chemistry makes it easy to load them with pharmaceutics and promote them to be theranostic nanosystems. Iron oxide nanoparticles, quantum dots, carbon nanotubes, gold nanoparticles and silica nanoparticles, have been previously well investigated in the imaging setting and are candidate nanoplatforms for building up nanoparticle-based theranostics. In the current article, we will outline the progress along this line, organized by the category of the core materials. We will focus on construction strategies and will discuss the challenges and opportunities associated with this emerging technology. PMID:20691229

  9. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for... Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. (a) Agents....

  10. BNCT: a promising area of research?

    NASA Astrophysics Data System (ADS)

    Gahbauer, Reinhard; Gupta, N.; Blue, T.; Goodman, J.; Grecula, J.; Soloway, A. H.; Wambersie, A.

    1997-02-01

    The renewed interest in boron neutron capture therapy (BNCT) is driven mainly by the disappointing progress in the treatment of brain tumors by other modalities over the last decades. Even though molecular biology newer drugs and strategies may promise better results in the future, BNCT is an attractive approach. Brain tumors kill by local growth and not be metastases. Boron can be delivered to the tumor while normal brain is protected by the blood brain barrier, which can be disrupted to the degree desired. Tumor selectivity can be obtained not only by improved drug barrier, which can be disrupted to the degree desired. Tumor selectivity can be obtained not only by improved drug delivery but also by restricting the capture reaction to the region of interest by targeted radiation. Both boron drug and thermal neutrons alone are to some extent innocuous to tumor and normal tissues in this binary form of therapy. The pattern of treatment failure from uncontrolled primary tumor, the blood brain barrier protection of normal surrounding tissue and the limited range of epithermal neutrons explain why brain tumors are the main focus of BNCT research.

  11. Uterine transplantation: a promising surrogate to surrogacy?

    PubMed

    Grynberg, Michael; Ayoubi, Jean-Marc; Bulletti, Carlo; Frydman, Rene; Fanchin, Renato

    2011-03-01

    Infertility due to the inability of the uterus to carry a pregnancy ranks among the most unresolved issues in reproductive medicine. It affects millions of women worldwide who have congenital or acquired uterine affections, often requiring hysterectomy, and potentially represents a considerable fraction of the general infertile population. Patients suffering from severe uterine infertility are currently compelled to go through gestational surrogacy or adoption; both approaches, unfortunately, deprive them of the maternal experience of pregnancy and birth. Uterine transplantation represents an outstanding, yet complex, perspective to alleviating definitive uterine infertility. In the past decades, a number of scientific experiments conducted both in animals and women, focusing on uterine transplantation, have led to promising results. Collectively, these findings undoubtedly constitute a sound basis to clinically apply uterine transplantation in the near future. This paper is, however, an overview not only of the extent and limitations of accumulated scientific knowledge on uterine transplantation, but also its ethical implications, in an effort to define the actual place of such an approach among the therapeutic arsenal for alleviating infertility. PMID:21401629

  12. Nanoparticles: a promising therapeutic approach in atherosclerosis.

    PubMed

    Antoniades, Charalambos; Psarros, Costantinos; Tousoulis, Dimitris; Bakogiannis, Constantinos; Shirodaria, Cheerag; Stefanadis, Christodoulos

    2010-10-01

    Coronary atherosclerosis is the largest cause of mortality and morbidity in industrialised countries. Despite recent advances in medical therapies, the prevention and treatment of atherosclerosis remain suboptimal. Atherosclerosis is considered to be a chronic inflammatory disease of the arterial wall, involving the accumulation of macrophages and excess low density lipoproteins (LDL), the formation of foam cells which create the atheromatous plaque, resulting in stenosis, aneurysm and plaque rupture leading to acute coronary events. Every step in the atherogenesis process is a potential therapeutic target for both the prevention and regression of atherosclerosis. A novel approach is the use of nanoparticles containing drugs, providing new perspectives in targeted modification of these pathways. Nanoparticles are ultrafine particles sized between 1-100 nm. By using specific methods, nanoparticles can be filled with drugs and achieve targeted drug delivery near the diseased area. In this review article we describe the basic actions of nanoparticles, and we discuss their potential applications in atherosclerosis. We also discuss their advantages and we expose the existing toxicity issues, making it clear however, that the use of nanoparticles is one of the most promising therapeutic strategies against atherosclerosis.

  13. Immunocytokines: a promising approach to cancer immunotherapy.

    PubMed

    Lode, H N; Xiang, R; Becker, J C; Gillies, S D; Reisfeld, R A

    1998-12-01

    Recombinant antibody-cytokine fusion proteins are immunocytokines that achieve high cytokine concentrations in the tumor microenvironment and thereby effectively stimulate cellular immune responses against malignancies. The activation and expansion of immune effector cells, such as CD8+ T lymphocytes, by interleukin-2 immunocytokines resulted in the eradication of established pulmonary and hepatic metastases of murine melanoma and colorectal carcinoma in syngeneic mouse models. These immunocytokines were equally effective in eliminating established bone marrow and liver metastases of murine neuroblastoma by activating natural killer cells. The effective eradication of metastases by immunocytokines resulted in significant prolongation in life span of mice over that of controls receiving equivalent mixtures of antibody and interleukin-2, which failed to reduce the growth of disseminated metastases. Proof of concept was established, indicating that immunocytokine-induced activation and expansion of immune effector cells in the tumor microenvironment can effectively eradicate established tumor metastases. This promising new approach to cancer immunotherapy may lead to clinical applications that improve treatment of cancer patients with minimal residual disease in an adjuvant setting.

  14. The Renewed Promise of Medical Informatics.

    PubMed

    van Bemmel, J H; McCray, A T

    2016-05-20

    The promise of the field of Medical Informatics has been great and its impact has been significant. In 1999, the Yearbook editors of the International Medical Informatics Association (IMIA) - also the authors of the present paper - sought to assess this impact by selecting a number of seminal papers in the field, and asking experts to comment on these articles. In particular, it was requested whether and how the expectations, represented by these papers, had been fulfilled since their publication several decades earlier. Each expert was also invited to comment on what might be expected in the future. In the present paper, these areas are briefly reviewed again. Where did these early papers have an impact and where were they not as successful as originally expected? It should be noted that the extraordinary developments in computer technology observed in the last two decades could not have been foreseen by these early researchers. In closing, some of the possibilities and limitations of research in medical informatics are outlined in the context of a framework that considers six levels of computer applications in medicine and health care. For each level, some predictions are made for the future, concluded with thoughts on fruitful areas for ongoing research in the field.

  15. Panspermia: A promising field of research

    NASA Astrophysics Data System (ADS)

    Henrique Rampelotto, Pabulo

    Although Panspermia -the hypothesis that life migrates naturally through space -has been raised many times along the human history, due to lack of any validation it remained merely speculative until few decades ago. It is only with the recent discoveries and advances from different fields of research that Panspermia has been given serious scientific consideration. The natural movement of material from planetary surface to planetary surface has been explored and the mechanisms are well established. A variety of studies demonstrate that microorganisms can survive under extreme conditions such as ultracentrifugation, hypervelocity, shock pressure, high temperature variations, vacuum and different ultraviolet and ionizing radiation intensities, which simulate the conditions experienced by microbes during the ejection from one planet, the journey through space as well as the impact in another planet. The discovery of potential habitable environments such as the satellites of Jupiter and Saturn expands the possibility of transfer of life within the Solar System. Consequently, studies of natural transfer of biological material occurring between satellites have been developed. Furthermore, the probability of interplanetary transfer of life out the Solar System has been explored. Therefore, in the last few decades, most of the major barriers against the acceptance of this hypothesis have been demolished and Panspermia reemerges as a promising field of research.

  16. Justicidin B: A Promising Bioactive Lignan.

    PubMed

    Hemmati, Shiva; Seradj, Hassan

    2016-01-01

    Adverse effects and drug resistance to the current onchopharmacologicals have increased the demand for alternative novel therapeutics. We herein introduce justicidin B, an arylnaphthalen lignan isolated from different plant origins, especially Justicia, Phyllanthus, Haplophyllum and Linum species. This cyclolignan exhibits a wide array of biological properties ranges from piscicidal to antifungal, antiviral and antibacterial activities. Activity against Trypanosoma brucei makes justicidin B a potential antiprotozoal agent for the treatment of neglected tropical diseases. Pharmacological properties like antiplatelet, anti-inflammatory and bone resorption inhibition have been also attributed to justicidin B. This compound is a potent cytotoxic substance on several cell lines, especially chronic myeloid and chronic lymphoid leukemia. Pharmacological values, natural variation, as well as biotechnological production of justicidin B by plant cell, tissue and organ culture are also described in this review. Chemical characteristics and chromatographic methods to identify justicidin B and its biosynthetic pathway have been discussed. Different approaches to the total synthesis of justicidin B are compared. This review would shed light on the role of justicidin B as an intriguing natural compound and provides a chance to optimize conditions for industrial applications. PMID:27347906

  17. Agent Concept for Intelligent Distributed Coordination in the Electric Power Grid

    SciTech Connect

    SMATHERS, DOUGLAS C.; GOLDSMITH, STEVEN Y.

    2001-03-01

    Intelligent agents and multi-agent systems promise to take information management for real-time control of the power grid to a new level. This report presents our concept for intelligent agents to mediate and coordinate communications between Control Areas and Security Coordinators for real-time control of the power grid. An appendix describes the organizations and publications that deal with agent technologies.

  18. Detecting biological warfare agents.

    PubMed

    Song, Linan; Ahn, Soohyoun; Walt, David R

    2005-10-01

    We developed a fiber-optic, microsphere-based, high-density array composed of 18 species-specific probe microsensors to identify biological warfare agents. We simultaneously identified multiple biological warfare agents in environmental samples by looking at specific probe responses after hybridization and response patterns of the multiplexed array.

  19. Travel Agent Course Outline.

    ERIC Educational Resources Information Center

    British Columbia Dept. of Education, Victoria.

    Written for college entry-level travel agent training courses, this course outline can also be used for inservice training programs offered by travel agencies. The outline provides information on the work of a travel agent and gives clear statements on what learners must be able to do by the end of their training. Material is divided into eight…

  20. Change Agent Survival Guide

    ERIC Educational Resources Information Center

    Dunbar, Folwell L.

    2011-01-01

    Consulting is a rough racket. Only a tarantula hair above IRS agents, meter maids and used car sales people, the profession is a prickly burr for slings and arrows. Throw in education, focus on dysfunctional schools and call oneself a "change agent," and this bad rap all but disappears. Unfortunately, though, consulting/coaching/mentoring in…

  1. ShowMe3D

    SciTech Connect

    Sinclair, Michael B

    2012-01-05

    ShowMe3D is a data visualization graphical user interface specifically designed for use with hyperspectral image obtained from the Hyperspectral Confocal Microscope. The program allows the user to select and display any single image from a three dimensional hyperspectral image stack. By moving a slider control, the user can easily move between images of the stack. The user can zoom into any region of the image. The user can select any pixel or region from the displayed image and display the fluorescence spectrum associated with that pixel or region. The user can define up to 3 spectral filters to apply to the hyperspectral image and view the image as it would appear from a filter-based confocal microscope. The user can also obtain statistics such as intensity average and variance from selected regions.

  2. "Show me" bioethics and politics.

    PubMed

    Christopher, Myra J

    2007-10-01

    Missouri, the "Show Me State," has become the epicenter of several important national public policy debates, including abortion rights, the right to choose and refuse medical treatment, and, most recently, early stem cell research. In this environment, the Center for Practical Bioethics (formerly, Midwest Bioethics Center) emerged and grew. The Center's role in these "cultural wars" is not to advocate for a particular position but to provide well researched and objective information, perspective, and advocacy for the ethical justification of policy positions; and to serve as a neutral convener and provider of a public forum for discussion. In this article, the Center's work on early stem cell research is a case study through which to argue that not only the Center, but also the field of bioethics has a critical role in the politics of public health policy.

  3. ShowMe3D

    2012-01-05

    ShowMe3D is a data visualization graphical user interface specifically designed for use with hyperspectral image obtained from the Hyperspectral Confocal Microscope. The program allows the user to select and display any single image from a three dimensional hyperspectral image stack. By moving a slider control, the user can easily move between images of the stack. The user can zoom into any region of the image. The user can select any pixel or region from themore » displayed image and display the fluorescence spectrum associated with that pixel or region. The user can define up to 3 spectral filters to apply to the hyperspectral image and view the image as it would appear from a filter-based confocal microscope. The user can also obtain statistics such as intensity average and variance from selected regions.« less

  4. RDoC: Translating promise into progress.

    PubMed

    Patrick, Christopher J; Hajcak, Greg

    2016-03-01

    As highlighted by articles in the current special issue, the RDoC initiative holds promise for advancing understanding of mental health problems. However, the initiative is at its early stages and it remains unclear what level of progress can be achieved and how quickly. In this closing article, we identify major challenges facing RDoC and propose concrete approaches to addressing these challenges, including (a) clearer specification of clinical problems for study, with use of symptom dimensions from integrative dimensional models of psychopathology as provisional, modifiable referents; (b) encouragement of research on a distinct set of traits corresponding to process constructs from the RDoC matrix-those represented across animal, child temperament, and adult personality literatures-to serve as interfaces between matrix constructs and clinical problems; (c) an emphasis in the near term on use of proximal units of analysis in RDoC studies-in particular, on physiological, behavioral, and self-report measures of matrix constructs (examined as states or traits, or both); (d) inclusion of a clear ontogenetic-developmental component in RDoC research projects; (e) routine analysis of the psychometric properties of nonreport (e.g., physiological, task-behavioral) variables, including systematic evaluation of their reliability and convergent-discriminant validity; (f) modification of existing grant review criteria to prioritize replication and synergy in RDoC investigative work; and (g) creation of a cumulative data network system (RDoC-DataWeb) to encourage and facilitate coordination of research efforts across RDoC research groups.

  5. Alcoholism research: delivering on the promise.

    PubMed Central

    Goodwin, F K

    1988-01-01

    Prospects for research advances in alcoholism are very promising, because of the explosion in the neurosciences and advances in epidemiology and typology of the disorder. For example, the field is now ready for molecular genetics studies of the early onset form of alcoholism that is transmitted from father to son with high penetrance. Leading neuroscientists are being recruited into alcoholism research. Paradoxically, this time of new hope coincides with challenges to the scientific enterprise, such as the animal rights movement and impatience with the scientific process in the face of the public health emergencies represented by acquired immunodeficiency syndrome (AIDS) and drug abuse. The emergence of genetically based subtypes of alcoholism suggests that at least two discrete illness processes are involved. Mounting evidence from spinal fluid studies has rekindled interest in a key role for serotonin in the early onset form of alcoholism. One hypothesis now being explored is that genetically low brain serotonin function may be part of the predisposition to this form of alcoholism. It is known that acute alcohol intake transiently increases brain serotonin turnover. Thus, drinking might be viewed as an attempt to correct a deficit, only to produce further serotonin depletion as the drug's effect wears off, setting up a vicious cycle of repeated attempts to self-medicate. Impulsive, violent, and suicidal behavior as well as alcohol abuse are associated with the low brain serotonin activity. Persons with these problems suffer from circadian rhythm and glucose metabolism disturbances that may also be mediated by serotonin. New pharmacological probes are now available to tease out the mechanisms of altered serotonin function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2847208

  6. Standard Agent Framework 1

    1999-04-06

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4)more » Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.« less

  7. How do agents represent?

    NASA Astrophysics Data System (ADS)

    Ryan, Alex

    Representation is inherent to the concept of an agent, but its importance in complex systems has not yet been widely recognised. In this paper I introduce Peirce's theory of signs, which facilitates a definition of representation in general. In summary, representation means that for some agent, a model is used to stand in for another entity in a way that shapes the behaviour of the agent with respect to that entity. Representation in general is then related to the theories of representation that have developed within different disciplines. I compare theories of representation from metaphysics, military theory and systems theory. Additional complications arise in explaining the special case of mental representations, which is the focus of cognitive science. I consider the dominant theory of cognition — that the brain is a representational device — as well as the sceptical anti-representational response. Finally, I argue that representation distinguishes agents from non-representational objects: agents are objects capable of representation.

  8. Emerging Cancer Vaccines: The Promise of Genetic Vectors

    PubMed Central

    Aurisicchio, Luigi; Ciliberto, Gennaro

    2011-01-01

    Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost. PMID:24212974

  9. Applying tattoo dye as a third-harmonic generation contrast agent for in vivo optical virtual biopsy of human skin.

    PubMed

    Tsai, Ming-Rung; Lin, Chen-Yu; Liao, Yi-Hua; Sun, Chi-Kuang

    2013-02-01

    Third-harmonic generation (THG) microscopy has been reported to provide intrinsic contrast in elastic fibers, cytoplasmic membrane, nucleus, actin filaments, lipid bodies, hemoglobin, and melanin in human skin. For advanced molecular imaging, exogenous contrast agents are developed for a higher structural or molecular specificity. We demonstrate the potential of the commonly adopted tattoo dye as a THG contrast agent for in vivo optical biopsy of human skin. Spectroscopy and microscopy experiments were performed on cultured cells with tattoo dyes, in tattooed mouse skin, and in tattooed human skin to demonstrate the THG enhancement effect. Compared with other absorbing dyes or nanoparticles used as exogenous THG contrast agents, tattoo dyes are widely adopted in human skin so that future clinical biocompatibility evaluation is relatively achievable. Combined with the demonstrated THG enhancement effect, tattoo dyes show their promise for future clinical imaging applications. PMID:23389681

  10. Applying tattoo dye as a third-harmonic generation contrast agent for in vivo optical virtual biopsy of human skin

    NASA Astrophysics Data System (ADS)

    Tsai, Ming-Rung; Lin, Chen-Yu; Liao, Yi-Hua; Sun, Chi-Kuang

    2013-02-01

    Third-harmonic generation (THG) microscopy has been reported to provide intrinsic contrast in elastic fibers, cytoplasmic membrane, nucleus, actin filaments, lipid bodies, hemoglobin, and melanin in human skin. For advanced molecular imaging, exogenous contrast agents are developed for a higher structural or molecular specificity. We demonstrate the potential of the commonly adopted tattoo dye as a THG contrast agent for in vivo optical biopsy of human skin. Spectroscopy and microscopy experiments were performed on cultured cells with tattoo dyes, in tattooed mouse skin, and in tattooed human skin to demonstrate the THG enhancement effect. Compared with other absorbing dyes or nanoparticles used as exogenous THG contrast agents, tattoo dyes are widely adopted in human skin so that future clinical biocompatibility evaluation is relatively achievable. Combined with the demonstrated THG enhancement effect, tattoo dyes show their promise for future clinical imaging applications.

  11. 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

  12. Petri Nets as Modeling Tool for Emergent Agents

    NASA Technical Reports Server (NTRS)

    Bergman, Marto

    2004-01-01

    Emergent agents, those agents whose local interactions can cause unexpected global results, require a method of modeling that is both dynamic and structured Petri Nets, a modeling tool developed for dynamic discrete event system of mainly functional agents, provide this, and have the benefit of being an established tool. We present here the details of the modeling method here and discuss how to implement its use for modeling agent-based systems. Petri Nets have been used extensively in the modeling of functional agents, those agents who have defined purposes and whose actions should result in a know outcome. However, emergent agents, those agents who have a defined structure but whose interaction causes outcomes that are unpredictable, have not yet found a modeling style that suits them. A problem with formally modeling emergent agents that any formal modeling style usually expects to show the results of a problem and the results of problems studied using emergent agents are not apparent from the initial construction. However, the study of emergent agents still requires a method to analyze the agents themselves, and have sensible conversation about the differences and similarities between types of emergent agents. We attempt to correct this problem by applying Petri Nets to the characterization of emergent agents. In doing so, the emergent properties of these agents can be highlighted, and conversation about the nature and compatibility of the differing methods of agent creation can begin.

  13. Molecularly Targeted Agents as Radiosensitizers in Cancer Therapy—Focus on Prostate Cancer

    PubMed Central

    Alcorn, Sara; Walker, Amanda J.; Gandhi, Nishant; Narang, Amol; Wild, Aaron T.; Hales, Russell K.; Herman, Joseph M.; Song, Danny Y.; DeWeese, Theodore L.; Antonarakis, Emmanuel S.; Tran, Phuoc T.

    2013-01-01

    As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts to improve the therapeutic ratio of radiation by technologic and pharmacologic means have led to important advances in cancer care. One promising approach is to combine molecularly targeted systemic agents with radiotherapy to improve tumor response rates and likelihood of durable control. This review first explores the limitations of preclinical studies as well as barriers to successful implementation of clinical trials with radiosensitizers. Special considerations related to and recommendations for the design of preclinical studies and clinical trials involving molecularly targeted agents combined with radiotherapy are provided. We then apply these concepts by reviewing a representative set of targeted therapies that show promise as radiosensitizers in the treatment of prostate cancer. PMID:23863691

  14. Casimir experiments showing saturation effects

    SciTech Connect

    Sernelius, Bo E.

    2009-10-15

    We address several different Casimir experiments where theory and experiment disagree. First out is the classical Casimir force measurement between two metal half spaces; here both in the form of the torsion pendulum experiment by Lamoreaux and in the form of the Casimir pressure measurement between a gold sphere and a gold plate as performed by Decca et al.; theory predicts a large negative thermal correction, absent in the high precision experiments. The third experiment is the measurement of the Casimir force between a metal plate and a laser irradiated semiconductor membrane as performed by Chen et al.; the change in force with laser intensity is larger than predicted by theory. The fourth experiment is the measurement of the Casimir force between an atom and a wall in the form of the measurement by Obrecht et al. of the change in oscillation frequency of a {sup 87}Rb Bose-Einstein condensate trapped to a fused silica wall; the change is smaller than predicted by theory. We show that saturation effects can explain the discrepancies between theory and experiment observed in all these cases.

  15. Trematode hemoglobins show exceptionally high oxygen affinity.

    PubMed

    Kiger, L; Rashid, A K; Griffon, N; Haque, M; Moens, L; Gibson, Q H; Poyart, C; Marden, M C

    1998-08-01

    Ligand binding studies were made with hemoglobin (Hb) isolated from trematode species Gastrothylax crumenifer (Gc), Paramphistomum epiclitum (Pe), Explanatum explanatum (Ee), parasitic worms of water buffalo Bubalus bubalis, and Isoparorchis hypselobagri (Ih) parasitic in the catfish Wallago attu. The kinetics of oxygen and carbon monoxide binding show very fast association rates. Whereas oxygen can be displaced on a millisecond time scale from human Hb at 25 degrees C, the dissociation of oxygen from trematode Hb may require a few seconds to over 20 s (for Hb Pe). Carbon monoxide dissociation is faster, however, than for other monomeric hemoglobins or myoglobins. Trematode hemoglobins also show a reduced rate of autoxidation; the oxy form is not readily oxidized by potassium ferricyanide, indicating that only the deoxy form reacts rapidly with this oxidizing agent. Unlike most vertebrate Hbs, the trematodes have a tyrosine residue at position E7 instead of the usual distal histidine. As for Hb Ascaris, which also displays a high oxygen affinity, the trematodes have a tyrosine in position B10; two H-bonds to the oxygen molecule are thought to be responsible for the very high oxygen affinity. The trematode hemoglobins display a combination of high association rates and very low dissociation rates, resulting in some of the highest oxygen affinities ever observed.

  16. Human absorbed dose estimation for a new (175)Yb-phosphonate based on rats data: Comparison with similar bone pain palliation agents.

    PubMed

    Vaez-Tehrani, Mahdokht; Zolghadri, Samaneh; Yousefnia, Hassan; Afarideh, Hossein

    2016-09-01

    In this work, the absorbed dose to human organs for (175)Yb-BPAMD was evaluated based on the biodistribution studies in rats. The results showed that the bone surface would receive the highest absorbed dose after injection of (175)Yb-BPAMD with 13.32mGy/MBq, while the other organs receive insignificant absorbed dose. Also, the comparison of (175)Yb-BPAMD with other therapeutic phosphonate complexes demonstrated noticeable characteristics for this new agent. Generally, based on the obtained results, (175)Yb-BPAMD can be considered as a promising agent for bone pain palliative therapy in near future. PMID:27337650

  17. Dynamically sequencing an animated pedagogical agent

    SciTech Connect

    Stone, B.A.; Lester, J.C.

    1996-12-31

    One of the most promising opportunities introduced by rapid advances in knowledge-based learning environments and multimedia technologies is the possibility of creating animated pedagogical agents. These agents should exhibit three properties: timely domain coverage (they should clearly communicate fundamental concepts and relationships within the allotted time); contextuality (they should provide explanations in appropriate problem-solving contexts); and continuity (their activities and utterances should be pedagogically, visually, and aurally coherent). We have developed the coherence-structured behavior space approach to creating animated pedagogical agents. This is a two-step approach. First, we design a behavior space of animation and audio segments that are structured by prerequisite relationships and a continuity metric. Second, we navigate coherent paths through the space to dynamically sequence behaviors. This creates seamless global behaviors that communicate fundamental knowledge and provide contextualized problem-solving advice. The coherence-structured behavior space approach has been implemented in Herman the Bug, an animated pedagogical agent for Design-A-Plant, a knowledge-based learning environment for botanical anatomy and physiology. Formative evaluations of the agent with middle school students are encouraging.

  18. Biological warfare agents.

    PubMed

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-07-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies.

  19. Biological warfare agents

    PubMed Central

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-01-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies. PMID:21829313

  20. Hypoxia targeted carbon nanotubes as a sensitive contrast agent for photoacoustic imaging of tumors

    NASA Astrophysics Data System (ADS)

    Zanganeh, Saeid; Aguirre, Andres; Biswal, Nrusingh C.; Pavlik, Christopher; Smith, Michael B.; Alqasemi, Umar; Li, Hai; Zhu, Quing

    2011-03-01

    Development of new and efficient contrast agents is of fundamental importance to improve detection sensitivity of smaller lesions. Within the family of nanomaterials, carbon nanotubes (CNT) not only have emerged as a new alternative and efficient transporter and translocater of therapeutic molecules but also as a photoacoustic molecular imaging agent owing to its strong optical absorption in the near-infrared region. Drugs, Antibodies and nucleic acids could functionalize the CNT and prepare an appropriate system for delivering the cargos to cells and organs. In this work, we present a novel photoacoustic contrast agent which is based on a unique hypoxic marker in the near infrared region, 2-nitroimidazole -bis carboxylic acid derivative of Indocyanine Green conjugated to single walled carbon nanotube (SWCNT-2nitroimidazole-ICG). The 2-nitroimidazole-ICG has an absorption peak at 755 nm and an extinction coefficient of 20,5222 M-1cm-1. The conjugation of this marker with SWCNT shows more than 25 times enhancement of optical absorption of carbon nanotubes in the near infrared region. This new conjugate has been optically evaluated and shows promising results for high contrast photoacoustic imaging of deeply located tumors. The conjugate specifically targets tumor hypoxia, an important indicator of tumor metabolism and tumor therapeutic response. The detection sensitivity of the new contrast agent has been evaluated in-vitro cell lines and with in-vivo tumors in mice.

  1. Mimas Showing False Colors #1

    NASA Technical Reports Server (NTRS)

    2005-01-01

    False color images of Saturn's moon, Mimas, reveal variation in either the composition or texture across its surface.

    During its approach to Mimas on Aug. 2, 2005, the Cassini spacecraft narrow-angle camera obtained multi-spectral views of the moon from a range of 228,000 kilometers (142,500 miles).

    The image at the left is a narrow angle clear-filter image, which was separately processed to enhance the contrast in brightness and sharpness of visible features. The image at the right is a color composite of narrow-angle ultraviolet, green, infrared and clear filter images, which have been specially processed to accentuate subtle changes in the spectral properties of Mimas' surface materials. To create this view, three color images (ultraviolet, green and infrared) were combined into a single black and white picture that isolates and maps regional color differences. This 'color map' was then superimposed over the clear-filter image at the left.

    The combination of color map and brightness image shows how the color differences across the Mimas surface materials are tied to geological features. Shades of blue and violet in the image at the right are used to identify surface materials that are bluer in color and have a weaker infrared brightness than average Mimas materials, which are represented by green.

    Herschel crater, a 140-kilometer-wide (88-mile) impact feature with a prominent central peak, is visible in the upper right of each image. The unusual bluer materials are seen to broadly surround Herschel crater. However, the bluer material is not uniformly distributed in and around the crater. Instead, it appears to be concentrated on the outside of the crater and more to the west than to the north or south. The origin of the color differences is not yet understood. It may represent ejecta material that was excavated from inside Mimas when the Herschel impact occurred. The bluer color of these materials may be caused by subtle differences in

  2. Dioxin, agent orange

    SciTech Connect

    Gough, M.

    1986-01-01

    This book presents information on the following topics: dioxin, a prevalent problem; nobody wanted dioxin; agent organe and Vietnam; what we know about and may learn about agent orange and Veterans' health; agent organe and birth defects; dioxin in Missouri; 2, 4, 5-T: the U.S.' disappearing herbicide; Seveso: high-level environmental exposure; the nitro explosion; industrial exposures to dioxin; company behavior in the face of dioxin exposures; dioxin and specific cancers; animal tests of dioxin toxicity; dioxin decions; the present and the future.

  3. The Promise of a College Scholarship Transforms a District

    ERIC Educational Resources Information Center

    Ritter, Gary W.; Ash, Jennifer

    2016-01-01

    Promise programs are place-based scholarships, generally tied to a city or school district, offering near-universal access to all living in the "place." While Promise programs share some characteristics with other scholarship programs, they're unique because they seek to change communities and schools. Underlying such promise programs is…

  4. Design, synthesis, and biological evaluation of anti-EV71 agents.

    PubMed

    Li, Peng; Yang, Bailing; Hao, Fei; Wang, Ping; He, Haiying; Huang, Lei; Zhang, Xuan; Zhang, Shengbin; Peng, Xuanjia; Yin, Ke; Hu, Jiao; Chen, Xinsheng; Gu, Zhengxian; Wang, Li; Shen, Liang; Hu, Guoping; Li, Ning; Li, Jian; Chen, Shuhui; Xiao, Wei; Wang, Zhenzhong; Guo, Qingming; Chang, Xiujuan; Zhang, Lanjun; Cai, Qixu; Lin, Tianwei

    2016-07-15

    Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease (HFMD), which can spread its infections to the central nervous and other systems with severe consequences. In this article, design, chemical synthesis, and biological evaluation of various anti-EV71 agents which incorporate Michael acceptors are described. Further SAR study demonstrated that lactone type of Michael acceptor provided a new lead of anti-EV71 drug candidates with high anti-EV71 activity in cell-based assay and enhanced mouse plasma stability. One of the most potent compounds (2K, cell-based anti-EV71 EC50=0.028μM), showed acceptable stability profile towards mouse plasma, which resulted into promising pharmacokinetics in mouse via IP administration. PMID:27234148

  5. Design, synthesis, and biological evaluation of anti-EV71 agents.

    PubMed

    Li, Peng; Yang, Bailing; Hao, Fei; Wang, Ping; He, Haiying; Huang, Lei; Zhang, Xuan; Zhang, Shengbin; Peng, Xuanjia; Yin, Ke; Hu, Jiao; Chen, Xinsheng; Gu, Zhengxian; Wang, Li; Shen, Liang; Hu, Guoping; Li, Ning; Li, Jian; Chen, Shuhui; Xiao, Wei; Wang, Zhenzhong; Guo, Qingming; Chang, Xiujuan; Zhang, Lanjun; Cai, Qixu; Lin, Tianwei

    2016-07-15

    Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease (HFMD), which can spread its infections to the central nervous and other systems with severe consequences. In this article, design, chemical synthesis, and biological evaluation of various anti-EV71 agents which incorporate Michael acceptors are described. Further SAR study demonstrated that lactone type of Michael acceptor provided a new lead of anti-EV71 drug candidates with high anti-EV71 activity in cell-based assay and enhanced mouse plasma stability. One of the most potent compounds (2K, cell-based anti-EV71 EC50=0.028μM), showed acceptable stability profile towards mouse plasma, which resulted into promising pharmacokinetics in mouse via IP administration.

  6. The Promise of Wave Power (Invited)

    NASA Astrophysics Data System (ADS)

    Brekken, T.

    2010-12-01

    The solutions to today's energy challenges need to be explored through alternative, renewable and clean energy sources to enable diverse energy resource plans. An extremely abundant and promising source of energy exists in the world's oceans: it is estimated that if 0.2 % of the oceans' untapped energy could be harnessed, it could provide power sufficient for the entire world. Ocean energy exists in the forms of wave, tidal, marine currents, thermal (temperature gradient) and salinity. Among these forms, significant opportunities and benefits have been identified in the area of ocean wave energy extraction, i.e., harnessing the motion of the ocean waves, and converting that motion into electrical energy. Ocean wave energy refers to the kinetic and potential energy in the heaving motion of ocean waves. Wave energy is essentially concentrated solar energy (as is wind energy). The heating of the earth’s surface by the sun (with other complex processes) drives the wind, which in turn blows across the surface of the ocean to create waves. At each stage of conversion, the power density increases. Ocean wave power offers several attractive qualities, including high power density, low variability, and excellent forecastability. A typical large ocean wave propogates at around 12 m/s with very little attenuation across the ocean. If the waves can be detected several hundred kilometers off shore, there can be 10 hours or more of accurate forecast horizon. In fact, analysis has shown good forecast accuracy up to 48 hours in advance. Off the coast Oregon, the yearly average wave power is approximately 30 kW per meter of crestlength (i.e., unit length transverse to the direction of wave propagation and parallel to the shore.) This compares very favorably with power densities of solar and wind, which typically range in the several hundreds of Watts per square meter. Globally, the wave energy resource is stronger on the west coasts of large landmasses and increases in strength

  7. Rose garden promises of intelligent tutoring systems: Blossom or thorn

    NASA Technical Reports Server (NTRS)

    Shute, Valerie J.

    1991-01-01

    Intelligent tutoring systems (ITS) have been in existence for over a decade. However, few controlled evaluation studies have been conducted comparing the effectiveness of these systems to more traditional instruction methods. Two main promises of ITSs are examined: (1) Engender more effective and efficient learning in relation to traditional formats; and (2) Reduce the range of learning outcome measures where a majority of individuals are elevated to high performance levels. Bloom (1984) has referred to these as the two sigma problem; to achieve two standard deviation improvements with tutoring over traditional instruction methods. Four ITSs are discussed in relation to the two promises. These tutors have undergone systematic, controlled evaluations: (1) The LISP tutor (Anderson Farrell and Sauers, 1984); (2) Smithtown (Shute and Glaser, in press); (3) Sherlock (Lesgold, Lajoie, Bunzo and Eggan, 1990); and (4) The Pascal ITS (Bonar, Cunningham, Beatty and Well, 1988). Results show that these four tutors do accelerate learning with no degradation in final outcome. Suggestions for improvements to the design and evaluation of ITSs are discussed.

  8. The Perils and Promises of Praise

    ERIC Educational Resources Information Center

    Dweck, Carol S.

    2007-01-01

    Educators commonly believe that praising students' intelligence builds their confidence and motivation to learn and that students' inherent intelligence is the major cause of their school achievement. The author's research shows that, on the contrary, praising students' intelligence can be problematic. Praise is intricately connected to how…

  9. Adolescent Literacy Instruction: Policies and Promising Practices

    ERIC Educational Resources Information Center

    Lewis, Jill, Ed.; Moorman, Gary, Ed.

    2007-01-01

    This comprehensive resource explores how adolescence and academic achievement are defined within today's political context, examines the in-school potential of teens' out-of-school immersion in digital technologies and popular culture, and shows teachers how to embed comprehension strategies into classroom instruction. The book contains innovative…

  10. Riot Control Agents

    MedlinePlus

    ... your clothing, rapidly wash your entire body with soap and water, and get medical care as quickly ... agent from your skin with large amounts of soap and water. Washing with soap and water will ...

  11. Radioactive diagnostic agent

    SciTech Connect

    Shigematsu, A.; Aihara, M.; Matsuda, M.; Suzuki, A.; Tsuya, A.

    1984-02-07

    A radioactive diagnostic agent for renal cortex, adrenal cortex, myocardium, brain stem, spinal nerve, etc., which comprises as an essential component monoiodoacetic acid wherein the iodine atom is radioactive.

  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. Microtubule-binding agents: a dynamic field of cancer therapeutics

    PubMed Central

    Dumontet, Charles; Jordan, Mary Ann

    2010-01-01

    Preface Microtubules are dynamic filamentous cytoskeletal proteins that are an important therapeutic target in tumor cells. Microtubule binding agents have been part of the pharmacopoeia of cancer for decades, and until the advent of targeted therapy microtubules were the only alternative to DNA as a therapeutic target in cancer. The screening of a variety of botanical species and marine organisms has yielded promising new antitubulin agents with novel properties. Enhanced tumor specificity, reduced neurotoxicity, and insensitivity to chemoresistance mechanisms are the three main objectives in the current search for novel microtubule binding agents. PMID:20885410

  14. The pharmacologic approach to airway clearance: mucoactive agents.

    PubMed

    Rubin, Bruce K

    2006-01-01

    The term "mucoactive agent" refers to any medication used to improve the clearance of airway secretions. It is not synonymous with the word "mucolytic" as this strictly means a drug that decreases the viscosity of secretions. In many cases, decreased viscosity will adversely affect cough transport. For this reason many of the older mucolytic agents such as acetylcysteine are not effective for the therapy of lung disease and their use is not recommended. I review here the many classes of mucoactive agents and identify a number of medications with great promise for the treatment of chronic airway disease. PMID:16798570

  15. Identification of thiostrepton as a novel therapeutic agent that targets human colon cancer stem cells.

    PubMed

    Ju, S-Y; Huang, C-Y F; Huang, W-C; Su, Y

    2015-01-01

    Accumulating evidence shows that colorectal cancer stem cells (CRSCs) are largely responsible for the metastasis and relapse of colorectal cancer (CRC) after therapy. Hence, identifying new agents that specifically target CRSCs would help improve the effectiveness of current CRC therapies. To accelerate identification of agents targeting CRSCs, the Connectivity Map (CMap) approach was used. Among the top-ranked candidates, thiostrepton, a thiazole antibiotic, was selected for further investigation because of its known tumoricidal activity. Thiostrepton could selectively induce apoptosis in CRSC subpopulations in both parental HCT-15 and HT-29 human CRC lines as well as in EMT and chemoresistant clones derived from them. Further, we investigated its inhibitory effects on the sphere- and colony-forming capabilities of the aforementioned CRC lines. The in vitro inhibition of sphere and colony formation was associated with downregulation of various modulators of the stem cell phenotype. The combination of thiostrepton and oxaliplatin eradicated both CD44(+) HCT-15 and HT-29 cells more efficiently than either drug alone. FoxM1, an oncogenic transcription factor, was identified as a critical positive modulator of stemness and as the main target of thiostrepton in the CRC lines. This is the first report showing the selective killing of CRSCs by thiostrepton, which has been proposed to be a promising anti-neoplastic agent. On the basis of its synergism with oxaliplatin in killing CRSCs in vitro, if this activity is confirmed in vivo, thiostrepton may be a promising agent to be used clinically in combination with current chemotherapies to improve the efficacy of these regimens. PMID:26136074

  16. Interaction between some common genotoxic agents.

    PubMed

    Beckman, L; Nordenson, I

    1986-01-01

    The clastogenic effects of arsenic, lead and sulphur dioxide and the protective effect of selenium were studied in short-term lymphocyte cultures. The three agents selected are the major toxic substances in emissions from copper smelters. Cells from non-smoking, healthy individuals were exposed to individual agents and combinations of the four agents (sodium arsenite, lead acetate, sodium sulphite and sodium selenite) and the cells were analysed for chromosome aberrations and sister chromatide exchanges. Selenium showed an antagonistic (protective) effect against the other agents. No synergistic effects were found, and the interactions between arsenic, lead and sulphur dioxide were mainly antagonistic. These rather unexpected findings indicate that mixed exposure from copper smelters, and other mixed exposures where arsenic, lead and sulphur dioxide are involved, may cause less genetic damage than expected and that an adequate dietary supplement of selenium may reduce the genotoxic effects of these agents. PMID:3793119

  17. Bone-targeted agents in the treatment of lung cancer

    PubMed Central

    Silva, Shobha C.; Wilson, Caroline

    2015-01-01

    Over a third of patients with lung cancer will develop bone metastases during the course of their disease, resulting in symptoms of pain and immobility, and skeletal-related events (SREs) such as fracture, hypercalcaemia, surgery or radiotherapy to bones, and malignant spinal cord compression. These reduce quality of life and increase mortality. Preclinical research has identified the interactions between tumour cells and bone that are key to tumour cell survival and associated osteolysis. These data have led to the development of drugs to prevent osteoclast-mediated bone breakdown, such as zoledronic acid and denosumab, which are now licensed for use in patients with bone metastases from solid tumours. Both zoledronic acid and denosumab reduce the risk of SREs and increase time to first SRE, with minimal side effects. In addition, denosumab improved survival in patients with lung cancer compared with zoledronic acid. Ongoing trials are testing whether these drugs can prevent the development of bone metastases from lung cancer. New bone-targeted agents showing promise in breast and prostate cancer include radium-223, cabozantinib and Src inhibitors. These agents require further evaluation in patients with lung cancer. PMID:26136853

  18. Recombinant mumps virus as a cancer therapeutic agent

    PubMed Central

    Ammayappan, Arun; Russell, Stephen J; Federspiel, Mark J

    2016-01-01

    Mumps virus belongs to the family of Paramyxoviridae and has the potential to be an oncolytic agent. Mumps virus Urabe strain had been tested in the clinical setting as a treatment for human cancer four decades ago in Japan. These clinical studies demonstrated that mumps virus could be a promising cancer therapeutic agent that showed significant antitumor activity against various types of cancers. Since oncolytic virotherapy was not in the limelight until the beginning of the 21st century, the interest to pursue mumps virus for cancer treatment slowly faded away. Recent success stories of oncolytic clinical trials prompted us to resurrect the mumps virus and to explore its potential for cancer treatment. We have obtained the Urabe strain of mumps virus from Osaka University, Japan, which was used in the earlier human clinical trials. In this report we describe the development of a reverse genetics system from a major isolate of this Urabe strain mumps virus stock, and the construction and characterization of several recombinant mumps viruses with additional transgenes. We present initial data demonstrating these recombinant mumps viruses have oncolytic activity against tumor cell lines in vitro and some efficacy in preliminary pilot animal tumor models. PMID:27556105

  19. Iodine-125 metaraminol: A new platelet specific labeling agent

    SciTech Connect

    Ohmomo, Y.; Yokoyama, A.; Kawaii, K.; Horiuchi, K.; Saji, H.; Torizuka, K.

    1984-01-01

    In the search for a platelet specific labeling agent, Metaraminol (MA), which is a sympatomimetic amine used for the treatment of hypotension, cardiogenic shock and well recognized as a drug actively incorporated and accumulated in platelet, attracted the authors' attention. Using the classical chloramine-T iodination method, a high labeling efficiency near 98%, reaching a specific activity up to about 1000 Ci/mmole was obtained. Upon the harvest of platelet, only as platelet rich plasma (PRP), the labeling with this radiopharmaceutical was easily performed by incubation at 37/sup 0/C for 10 min. Labeling efficiency as high as 63.0 +- 3.1% at 24 x 10/sup 8/ cells/ml was obtained. In in-vitro studies, the unaltered state of I-125 MA labeled platelet, with their cellular functions fully retained was demonstrated. Pharmacological study indicated a specific incorporation of I-125 MA by active transport system similar to that of 5-HT, along with passive diffusion. Then the in-vivo study carried out in rabbits with induced thrombi on the femoral artery, showed rather rapid disappearance of the I-125 MA labeled autologous platelet radioactivity, from circulating blood reaching as high thrombus-to-blood activity ratio as 19.8+-4.3 within 30 min post-administration. This new platelet labeling agent, I-125 MA, has many advantages over the use of IN-111 oxine and holds considerable promise for thrombus imaging with single photon emission CT upon the availability of I-123 MA.

  20. PEGylated Copper Nanowires as a Novel Photothermal Therapy Agent.

    PubMed

    Li, Kuei-Chang; Chu, Hsun-Chen; Lin, Yow; Tuan, Hsing-Yu; Hu, Yu-Chen

    2016-05-18

    Metal nanowires are promising for their applications including electrical connectors, transparent conductive electrodes and conductive additives, but the use of metal nanowires as photothermal agents to convert light to heat has yet to be reported. Here we synthesized dispersible polyethylene glycol-coated (PEGylated) copper nanowires (CuNWs) and showed for the first time that PEGylated CuNWs were able to convert near-infrared (NIR, 808 nm) light into heat at a photothermal efficiency of 12.5%. The PEGylated CuNWs exhibited good reusability and enabled rapid temperature rise to >50 °C in 6 min by NIR irradiation. The PEGylated CuNWs were flexible and intertwined around the cancer cells, which, upon NIR irradiation, allowed for direct heat transmission to cells and effectively triggered cancer cell ablation in vitro. Intratumoral injection of PEGylated CuNWs into colon tumor-bearing mice and ensuing NIR irradiation for 6 min significantly raised the local temperature to >50 °C, induced necrosis, and suppressed tumor growth. Compared with other NIR light absorbing noble metal-based nanomaterials, PEGylated CuNWs are relatively easy to synthesize in both laboratory and large scales using the low cost copper. This study demonstrated the potential of PEGylated CuNWs as a new cost-effective photothermal agent, and paved a new avenue to using CuNWs for cancer therapy. PMID:27111420

  1. Thermoresponsive Acidic Microgels as Functional Draw Agents for Forward Osmosis Desalination.

    PubMed

    Hartanto, Yusak; Zargar, Masoumeh; Wang, Haihui; Jin, Bo; Dai, Sheng

    2016-04-19

    Thermoresponsive microgels with carboxylic acid functionalization have been recently introduced as an attractive draw agent for forward osmosis (FO) desalination, where the microgels showed promising water flux and water recovery performance. In this study, various comonomers containing different carboxylic acid and sulfonic acid functional groups were copolymerized with N-isopropylacrylamide (NP) to yield a series of functionalized thermoresponsive microgels possessing different acidic groups and hydrophobicities. The purified microgels were examined as the draw agents for FO application, and the results show the response of water flux and water recovery was significantly affected by various acidic comonomers. The thermoresponsive microgel with itaconic acid shows the best overall performance with an initial water flux of 44.8 LMH, water recovery up to 47.2% and apparent water flux of 3.1 LMH. This study shows that the incorporation of hydrophilic dicarboxylic acid functional groups into the microgels leads to the enhancement on water adsorption and overall performance. Our work elucidates in detail on the structure-property relationship of thermoresponsive microgels in their applications as FO draw agents and would be beneficial for future design and development of high performance FO desalination.

  2. Thermoresponsive Acidic Microgels as Functional Draw Agents for Forward Osmosis Desalination.

    PubMed

    Hartanto, Yusak; Zargar, Masoumeh; Wang, Haihui; Jin, Bo; Dai, Sheng

    2016-04-19

    Thermoresponsive microgels with carboxylic acid functionalization have been recently introduced as an attractive draw agent for forward osmosis (FO) desalination, where the microgels showed promising water flux and water recovery performance. In this study, various comonomers containing different carboxylic acid and sulfonic acid functional groups were copolymerized with N-isopropylacrylamide (NP) to yield a series of functionalized thermoresponsive microgels possessing different acidic groups and hydrophobicities. The purified microgels were examined as the draw agents for FO application, and the results show the response of water flux and water recovery was significantly affected by various acidic comonomers. The thermoresponsive microgel with itaconic acid shows the best overall performance with an initial water flux of 44.8 LMH, water recovery up to 47.2% and apparent water flux of 3.1 LMH. This study shows that the incorporation of hydrophilic dicarboxylic acid functional groups into the microgels leads to the enhancement on water adsorption and overall performance. Our work elucidates in detail on the structure-property relationship of thermoresponsive microgels in their applications as FO draw agents and would be beneficial for future design and development of high performance FO desalination. PMID:27055090

  3. Redesigning the DNA-Targeted Chromophore in Platinum–Acridine Anticancer Agents: A Structure–Activity Relationship Study

    PubMed Central

    Pickard, Amanda J.; Liu, Fang; Bartenstein, Thomas F.; Haines, Laura G.; Levine, Keith E.; Kucera, Gregory L.; Bierbach, Ulrich

    2014-01-01

    Platinum–acridine hybrid agents show low-nanomolar potency in chemoresistant non-small cell lung cancer (NSCLC), but high systemic toxicity in vivo. To reduce the promiscuous genotoxicity of these agents and improve their pharmacological properties, a modular build–click–screen approach was used to evaluate a small library of twenty hybrid agents containing truncated and extended chromophores of varying basicities. Selected derivatives were resynthesized and tested in five NSCLC cell lines representing large cell, squamous cell, and adenocarcinomas. 7-Aminobenz[c]acridine was identified as a promising scaffold in a hybrid agent (P1–B1) that maintained submicromolar activity in several of the DNA-repair proficient and p53-mutant cancer models, while showing improved tolerability in mice by 32-fold compared to the parent platinum–acridine (P1–A1). The distribution and DNA/RNA adduct levels produced by the acridine- and benz[c]acridine-based analogues in NCI-H460 cells (confocal microscopy, ICP-MS), and their ability to bind G-quadruplex forming DNA sequences (CD spectroscopy, HR-ESMS) were studied. P1–B1 emerges as a less genotoxic, more tolerable, and potentially more target-selective hybrid agent than P1–A1. PMID:25302716

  4. Chaotic neurodynamics for autonomous agents.

    PubMed

    Harter, Derek; Kozma, Robert

    2005-05-01

    Mesoscopic level neurodynamics study the collective dynamical behavior of neural populations. Such models are becoming increasingly important in understanding large-scale brain processes. Brains exhibit aperiodic oscillations with a much more rich dynamical behavior than fixed-point and limit-cycle approximation allow. Here we present a discretized model inspired by Freeman's K-set mesoscopic level population model. We show that this version is capable of replicating the important principles of aperiodic/chaotic neurodynamics while being fast enough for use in real-time autonomous agent applications. This simplification of the K model provides many advantages not only in terms of efficiency but in simplicity and its ability to be analyzed in terms of its dynamical properties. We study the discrete version using a multilayer, highly recurrent model of the neural architecture of perceptual brain areas. We use this architecture to develop example action selection mechanisms in an autonomous agent. PMID:15940987

  5. Hepatitis C virus: Promising discoveries and new treatments

    PubMed Central

    Bastos, Juliana Cristina Santiago; Padilla, Marina Aiello; Caserta, Leonardo Cardia; Miotto, Noelle; Vigani, Aline Gonzalez; Arns, Clarice Weis

    2016-01-01

    Despite advances in therapy, hepatitis C virus (HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants (quasispecies) allows the virus to escape control by antivirals. Historically, the combination of ribavirin and interferon therapy has represented the only treatment option for the disease. Currently, several new treatment options are emerging and are available to a large part of the affected population. In addition, the search for new substances with antiviral activity against HCV continues, promising future improvements in treatment. Researchers should consider the mutation capacity of the virus and the other variables that affect treatment success. PMID:27605875

  6. Hepatitis C virus: Promising discoveries and new treatments.

    PubMed

    Bastos, Juliana Cristina Santiago; Padilla, Marina Aiello; Caserta, Leonardo Cardia; Miotto, Noelle; Vigani, Aline Gonzalez; Arns, Clarice Weis

    2016-07-28

    Despite advances in therapy, hepatitis C virus (HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants (quasispecies) allows the virus to escape control by antivirals. Historically, the combination of ribavirin and interferon therapy has represented the only treatment option for the disease. Currently, several new treatment options are emerging and are available to a large part of the affected population. In addition, the search for new substances with antiviral activity against HCV continues, promising future improvements in treatment. Researchers should consider the mutation capacity of the virus and the other variables that affect treatment success.

  7. The promise of N-acetylcysteine in neuropsychiatry.

    PubMed

    Berk, Michael; Malhi, Gin S; Gray, Laura J; Dean, Olivia M

    2013-03-01

    N-Acetylcysteine (NAC) targets a diverse array of factors germane to the pathophysiology of multiple neuropsychiatric disorders including glutamatergic transmission, the antioxidant glutathione, neurotrophins, apoptosis, mitochondrial function, and inflammatory pathways. This review summarises the areas where the mechanisms of action of NAC overlap with known pathophysiological elements, and offers a précis of current literature regarding the use of NAC in disorders including cocaine, cannabis, and smoking addictions, Alzheimer's and Parkinson's diseases, autism, compulsive and grooming disorders, schizophrenia, depression, and bipolar disorder. There are positive trials of NAC in all these disorders, and although many of these require replication and are methodologically preliminary, this makes it one of the most promising drug candidates in neuropsychiatric disorders. The efficacy pattern of NAC interestingly shows little respect for the current diagnostic systems. Its benign tolerability profile, its action on multiple operative pathways, and the emergence of positive trial data make it an important target to investigate. PMID:23369637

  8. Hepatitis C virus: Promising discoveries and new treatments.

    PubMed

    Bastos, Juliana Cristina Santiago; Padilla, Marina Aiello; Caserta, Leonardo Cardia; Miotto, Noelle; Vigani, Aline Gonzalez; Arns, Clarice Weis

    2016-07-28

    Despite advances in therapy, hepatitis C virus (HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants (quasispecies) allows the virus to escape control by antivirals. Historically, the combination of ribavirin and interferon therapy has represented the only treatment option for the disease. Currently, several new treatment options are emerging and are available to a large part of the affected population. In addition, the search for new substances with antiviral activity against HCV continues, promising future improvements in treatment. Researchers should consider the mutation capacity of the virus and the other variables that affect treatment success. PMID:27605875

  9. Emerging neurotechnologies for lie-detection: promises and perils.

    PubMed

    Wolpe, Paul Root; Foster, Kenneth R; Langleben, Daniel D

    2010-10-01

    Detection of deception and confirmation of truth telling with conventional polygraphy raised a host of technical and ethical issues. Recently, newer methods of recording electromagnetic signals from the brain show promise in permitting the detection of deception or truth telling. Some are even being promoted as more accurate than conventional polygraphy. While the new technologies raise issues of personal privacy, acceptable forensic application, and other social issues, the focus of this paper is the technical limitations of the developing technology. Those limitations include the measurement validity of the new technologies, which remains largely unknown. Another set of questions pertains to the psychological paradigms used to model or constrain the target behavior. Finally, there is little standardization in the field, and the vulnerability of the techniques to countermeasures is unknown. Premature application of these technologies outside of research settings should be resisted, and the social conversation about the appropriate parameters of its civil, forensic, and security use should begin.

  10. Emerging neurotechnologies for lie-detection: promises and perils.

    PubMed

    Wolpe, Paul Root; Foster, Kenneth R; Langleben, Daniel D

    2005-01-01

    Detection of deception and confirmation of truth telling with conventional polygraphy raised a host of technical and ethical issues. Recently, newer methods of recording electromagnetic signals from the brain show promise in permitting the detection of deception or truth telling. Some are even being promoted as more accurate than conventional polygraphy. While the new technologies raise issues of personal privacy, acceptable forensic application, and other social issues, the focus of this paper is the technical limitations of the developing technology. Those limitations include the measurement validity of the new technologies, which remains largely unknown. Another set of questions pertains to the psychological paradigms used to model or constrain the target behavior. Finally, there is little standardization in the field, and the vulnerability of the techniques to countermeasures is unknown. Premature application of these technologies outside of research settings should be resisted, and the social conversation about the appropriate parameters of its civil, forensic, and security use should begin.

  11. Scrap tire recycling: Promising high value applications. Final report

    SciTech Connect

    Bauman, B.D.; Leskovyansky, P.J.; Drela, H.

    1993-11-01

    Surface modification of scrap tire rubber (rubber particles treated with chlorine gas) show promise for ameliorating the scrap tire problem (the treated rubber can be used as a component in high- performance, expensive polymer systems). The process has been proven in Phase I. Phase II covers market/applications, process development (Forberg-design mixer reactor was chosen), plant design, capital cost estimate, economics environmental/safety/health, and energy impact. Almost of the small amount of chlorine is consumed. The capital costs for a rubber particle treatment facility are attractive, being at least two orders of magnitude less than that of facilities for making new polymer materials. Large volume markets using treated rubber are needed. The amount of scrap rubber available is small compared to the polymers available for replacement. 7 tabs, 16 figs.

  12. Hepatitis C virus: Promising discoveries and new treatments

    PubMed Central

    Bastos, Juliana Cristina Santiago; Padilla, Marina Aiello; Caserta, Leonardo Cardia; Miotto, Noelle; Vigani, Aline Gonzalez; Arns, Clarice Weis

    2016-01-01

    Despite advances in therapy, hepatitis C virus (HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants (quasispecies) allows the virus to escape control by antivirals. Historically, the combination of ribavirin and interferon therapy has represented the only treatment option for the disease. Currently, several new treatment options are emerging and are available to a large part of the affected population. In addition, the search for new substances with antiviral activity against HCV continues, promising future improvements in treatment. Researchers should consider the mutation capacity of the virus and the other variables that affect treatment success.

  13. Lloydminster fireflood performance, modifications promise good recoveries. [Canadian oil fields

    SciTech Connect

    Fairfield, W.H.; White, P.D.

    1982-02-08

    Efforts to increase ultimate recovery by thermal methods began 16 years ago with steam huff-and-puff and displacement steam drive. These early efforts were not successful. The first in situ combustion drive, the Golden Lake Sparky Fireflood, was initiated 12 years ago and is the subject of this work. It consists of one 20-acre inverted five-spot pattern and two approximately 30-acre inverted seven-spots. All three patterns are currently operating, and the project shows promise of accomplishing recoveries in excess of 30%. It is currently being expanded to include two additional patterns. Field characteristics are discussed along with observations on combustion operations Sparky sands. A critique of the fireflood process is given and the oxygen fireflood - a modification to the fireflood process - is outlined. 4 refs.

  14. Imaging synaptic zinc: promises and perils.

    PubMed

    Kay, Alan R

    2006-04-01

    It is well established that some excitatory nerve terminals have high concentrations of Zn(2+) in their synaptic vesicles. For some time, it has been believed that synaptic Zn(2+) is released during neurotransmission and acts as a neuromodulator. Fluorescent Zn(2+) indicators that do not penetrate membranes offer the prospect of rendering the release of Zn(2+) visible. Here, I take a critical look at fluorimetric imaging experiments devised to determine whether Zn(2+) is released and show that they are particularly susceptible to artifacts. Moreover, I will argue that recent experiments suggest that, rather than being released, Zn(2+) is presented to the extracellular space firmly coordinated to presynaptic macromolecules.

  15. Topical agents for hair growth promotion: what is out there?

    PubMed

    Shamsaldeen, Omar S; Al Mubki, Thamer; Shapiro, Jerry

    2013-06-01

    Hair loss is a widespread complaint that carries a significant psychosocial burden for affected individuals. Androgenetic alopecia (AGA) is the predominant cause of hair loss seen in the dermatology clinic. Although a range of therapies are available, minoxidil remains the only approved topical treatment for AGA. Promising new topical agents are under current investigation. PMID:24310642

  16. Metformin: A Hopeful Promise in Aging Research.

    PubMed

    Novelle, Marta G; Ali, Ahmed; Diéguez, Carlos; Bernier, Michel; de Cabo, Rafael

    2016-03-01

    Even though the inevitable process of aging by itself cannot be considered a disease, it is directly linked to life span and is the driving force behind all age-related diseases. It is an undisputable fact that age-associated diseases are among the leading causes of death in the world, primarily in industrialized countries. During the last several years, an intensive search of antiaging treatments has led to the discovery of a variety of drugs that promote health span and/or life extension. The biguanide compound metformin is widely used for treating people with type 2 diabetes and appears to show protection against cancer, inflammation, and age-related pathologies. Here, we summarize the recent developments about metformin use in translational aging research and discuss its role as a potential geroprotector. PMID:26931809

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

    PubMed Central

    Marshall, Brandon D. L.; Galea, Sandro

    2015-01-01

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

  18. Agent independent task planning

    NASA Technical Reports Server (NTRS)

    Davis, William S.

    1990-01-01

    Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

  19. Sunscreening agents: a review.

    PubMed

    Latha, M S; Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B R

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents.

  20. Lean in healthcare: the unfilled promise?

    PubMed

    Radnor, Zoe J; Holweg, Matthias; Waring, Justin

    2012-02-01

    In an effort to improve operational efficiency, healthcare services around the world have adopted process improvement methodologies from the manufacturing sector, such as Lean Production. In this paper we report on four multi-level case studies of the implementation of Lean in the English NHS. Our results show that this generally involves the application of specific Lean 'tools', such as 'kaizen blitz' and 'rapid improvement events', which tend to produce small-scale and localised productivity gains. Although this suggests that Lean might not currently deliver the efficiency improvements desired in policy, the evolution of Lean in the manufacturing sector also reveals this initial focus on the 'tool level'. In moving to a more system-wide approach, however, we identify significant contextual differences between healthcare and manufacturing that result in two critical breaches of the assumptions behind Lean. First, the customer and commissioner in the private sector are the one and the same, which is essential in determining 'customer value' that drives process improvement activities. Second, healthcare is predominantly designed to be capacity-led, and hence there is limited ability to influence demand or make full use of freed-up resources. What is different about this research is that these breaches can be regarded as not being primarily 'professional' in origin but actually more 'organisational' and 'managerial' and, if not addressed could severely constrain Lean's impact on healthcare productivity at the systems level.

  1. Lean in healthcare: the unfilled promise?

    PubMed

    Radnor, Zoe J; Holweg, Matthias; Waring, Justin

    2012-02-01

    In an effort to improve operational efficiency, healthcare services around the world have adopted process improvement methodologies from the manufacturing sector, such as Lean Production. In this paper we report on four multi-level case studies of the implementation of Lean in the English NHS. Our results show that this generally involves the application of specific Lean 'tools', such as 'kaizen blitz' and 'rapid improvement events', which tend to produce small-scale and localised productivity gains. Although this suggests that Lean might not currently deliver the efficiency improvements desired in policy, the evolution of Lean in the manufacturing sector also reveals this initial focus on the 'tool level'. In moving to a more system-wide approach, however, we identify significant contextual differences between healthcare and manufacturing that result in two critical breaches of the assumptions behind Lean. First, the customer and commissioner in the private sector are the one and the same, which is essential in determining 'customer value' that drives process improvement activities. Second, healthcare is predominantly designed to be capacity-led, and hence there is limited ability to influence demand or make full use of freed-up resources. What is different about this research is that these breaches can be regarded as not being primarily 'professional' in origin but actually more 'organisational' and 'managerial' and, if not addressed could severely constrain Lean's impact on healthcare productivity at the systems level. PMID:21414703

  2. The unfulfilled promise of the antidepressant medications.

    PubMed

    Davey, Christopher G; Chanen, Andrew M

    2016-05-16

    Australia has one of the highest rates of antidepressant use in the world; it has more than doubled since 2000, despite evidence showing that the effectiveness of these medications is lower than previously thought. An increasing placebo response rate is a key reason for falling effectiveness, with the gap between response to medications and placebo narrowing. Psychotherapies are effective treatments, but recent evidence from high-quality studies suggests that their effectiveness is also modest. Combined treatment with medication and psychotherapy provides greater effectiveness than either alone. The number of patients receiving psychotherapy had been declining, although this trend is probably reversing with the Medicare Better Access to Mental Health Care initiative. Antidepressant medications still have an important role in the treatment of moderate to severe depression; they should be provided as part of an overall treatment plan that includes psychotherapy and lifestyle strategies to improve diet and increase exercise. When medications are prescribed, they should be used in a way that maximises their chance of effectiveness. PMID:27169968

  3. The Promised Land of Human Immunology

    PubMed Central

    Su, Laura F.; Han, Arnold; McGuire, Helen M.; Furman, David; Newell, Evan W.; Davis, Mark M.

    2016-01-01

    Advances in technology and data analysis have made it possible to take a new look at human immunology. These advances run the gamut from systems biology approaches, which are likely in the vanguard of how we can start “to put the pieces together” of immune function, to a deeper understanding of specific diseases and vaccines and the immune repertoire. In our own experience, we have also found that asking simple questions about human immunity has often given us very surprising answers, causing a rethink of established dogma. Thus, we have developed a new perspective on the nature of the αβ TCR repertoire and also the likely role of T-cell repertoire (TCR) cross-reactivity in generating T memory independent of specific antigen interactions. These findings show that human immunology is not just a necessary step for “translating” basic immunology to treat diseases or develop better vaccines, but is also an important complement to the inbred mouse model. PMID:24638855

  4. Lung cancer screening: promise and pitfalls.

    PubMed

    Berg, Christine D; Aberle, Denise R; Wood, Douglas E

    2012-01-01

    The results of the National Lung Screening Trial (NLST) have provided the medical community and American public with considerable optimism about the potential to reduce lung cancer mortality with imaging-based screening. Designed as a randomized trial, the NLST has provided the first evidence of screening benefit by showing a 20% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality with low dose helical computed tomography (LDCT) screening relative to chest X-ray. The major harms of LDCT screening include the potential for radiation-induced carcinogenesis; high false-positivity rates in individuals without lung cancer, and overdiagnosis. Following the results of the NLST, the National Comprehensive Cancer Network (NCCN) published the first of multiple lung cancer screening guidelines under development by major medical organizations. These recommendations amalgamated screening cohorts, practices, interpretations, and diagnostic follow-up based on the NLST and other published studies to provide guidance for the implementation of LDCT screening. There are major areas of opportunity to optimize implementation. These include standardizing practices in the screening setting, optimizing risk profiles for screening and for managing diagnostic evaluation in individuals with indeterminate nodules, developing interdisciplinary screening programs in conjunction with smoking cessation, and approaching all stakeholders systematically to ensure the broadest education and dissemination of screening benefits relative to risks. The incorporation of validated biomarkers of risk and preclinical lung cancer can substantially enhance the effectiveness screening programs. PMID:24451779

  5. The promise of ketamine for treatment-resistant depression: current evidence and future directions

    PubMed Central

    DeWilde, Kaitlin E.; Levitch, Cara F.; Murrough, James W.; Mathew, Sanjay J.; Iosifescu, Dan V.

    2014-01-01

    Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is a significant public health threat. Current treatments for MDD primarily consist of monoamine-targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant in MDD. We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with the NIMH Research Domain Criteria (RDoC) initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of other glutamatergic agents other than ketamine currently being tested as novel antidepressants. PMID:25649308

  6. Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises.

    PubMed

    Aragon-Ching, Jeanny B; Trump, Donald L

    2016-09-01

    Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.

  7. Advances in nanodiagnostic techniques for microbial agents.

    PubMed

    Syed, Muhammad Ali

    2014-01-15

    Infectious diseases account for millions of sufferings and deaths in both developing as well as developed countries with a substantial economic loss. Massive increase in world population and international travel has facilitated their spread from one part of the world to other areas, making them one of the most significant global health risks. Furthermore, detection of bioterrorism agents in water, food and environmental samples as well traveler's baggage is a great challenge of the time for security purpose. Prevention strategies against infectious agents demand rapid and accurate detection and identification of the causative agents with highest sensitivity which should be equally available in different parts of the globe. Similarly, rapid and early diagnosis of infectious diseases has always been indispensable for their prompt cure and management, which has stimulated scientists to develop highly sophisticated techniques over centuries and the efforts continue unabated. Conventional diagnostic techniques are time consuming, tedious, expensive, less sensitive, and unsuitable for field situations. Nanodiagnostic assays have been promising for early, sensitive, point-of-care and cost-effective detection of microbial agents. There has been an explosive research in this area of science in last two decades yielding highly fascinating results. This review highlights some of the advancements made in the field of nanotechnology based assays for microbial detection since 2005 along with providing the basic understanding. PMID:24012709

  8. For whom will the Bayesian agents vote?

    NASA Astrophysics Data System (ADS)

    Caticha, Nestor; Cesar, Jonatas; Vicente, Renato

    2015-04-01

    Within an agent-based model where moral classifications are socially learned, we ask if a population of agents behaves in a way that may be compared with conservative or liberal positions in the real political spectrum. We assume that agents first experience a formative period, in which they adjust their learning style acting as supervised Bayesian adaptive learners. The formative phase is followed by a period of social influence by reinforcement learning. By comparing data generated by the agents with data from a sample of 15000 Moral Foundation questionnaires we found the following. 1. The number of information exchanges in the formative phase correlates positively with statistics identifying liberals in the social influence phase. This is consistent with recent evidence that connects the dopamine receptor D4-7R gene, political orientation and early age social clique size. 2. The learning algorithms that result from the formative phase vary in the way they treat novelty and corroborative information with more conservative-like agents treating it more equally than liberal-like agents. This is consistent with the correlation between political affiliation and the Openness personality trait reported in the literature. 3. Under the increase of a model parameter interpreted as an external pressure, the statistics of liberal agents resemble more those of conservative agents, consistent with reports on the consequences of external threats on measures of conservatism. We also show that in the social influence phase liberal-like agents readapt much faster than conservative-like agents when subjected to changes on the relevant set of moral issues. This suggests a verifiable dynamical criterium for attaching liberal or conservative labels to groups.

  9. Scalp psoriasis: a promising natural treatment.

    PubMed

    Wollina, U; Hercogovấ, J; Fioranelli, M; Gianfaldoni, S; Chokoeva, A A; Tchernev, G; Tirant, M; Novotny, F; Roccia, M G; Maximov, G K; França, K; Lotti, T

    2016-01-01

    Psoriasis is a lifelong chronic inflammatory disease affecting 2-3% of the worldwide population. Scalp psoriasis is a particular form of psoriasis characterized by lesions on the scalp, which may occur isolated or in association with other skin lesions. The aim of this study was to investigate the efficacy and safeness of an innovative treatment of scalp psoriasis, which is based on the topical application of natural products. Fifty adult subjects with scalp psoriasis (23 females, 27 males) from different European dermatological centres were included in the study. Forty-six patients with severely infiltrated psoriatic lesions were invited to use the products of Dr Michaels® (Soratinex®), according to a three-phase application, twice a day (morning and evening). The other 4 patients followed a different regimen: after a shampoo in the evening, they applied the conditioner in the night and washed it in the morning with the cleansing gel. The application time of Dr Michaels® (Soratinex®) products was 8 weeks. The treatment was evaluated at 0, 1, 2, 3, 4, 5, 6, 7, and 8 weeks. The evaluation was based on the Psoriasis Scalp Severity Index (PSSI) and on a photographic analysis at each of the medical evaluation points. At the end of the study, all patients showed an outstanding improvement. Five patients referred a transient pruritus, which regressed spontaneously without discontinuing the application. No other side effects have been described. We observe that Dr Michaels® (Soratinex®) natural product family can be considered as a valid therapeutic tool for scalp psoriasis when considering the exclusion criteria. The tested products provided an outstanding improvement of lesions in all the patients, without side effects. PMID:27498666

  10. Topical therapy for psoriasis: a promising future. Focus on JAK and phosphodiesterase-4 inhibitors.

    PubMed

    Rafael, Adilia; Torres, Tiago

    2016-01-01

    Psoriasis is a common, chronic and disabling skin disorder affecting approximately 2% of the population, associated with significant negative impact on the patient's quality of life. Approximately 80% of those affected with psoriasis have mild-to-moderate forms and are usually treated with topical therapy, whereas phototherapy and systemic therapies are used for those with severe disease. In the past three decades, the major advances in psoriasis therapy have been in systemic agents for the treatment of moderate-to-severe psoriasis, particularly new immunomodulatory and biological molecules, while topical therapies have remained relatively unchanged over the past decades. Indeed, topical corticosteroids and vitamin D3 analogs are still the gold standard of therapy for mild-to-moderate psoriasis. Thus, there is a need to develop new and more effective topical agents in the short and long term, with a better efficacy and safety profile than corticosteroids and vitamin D3 analogs. Over the past five years, investigation into topical therapy has expanded, with exciting new drugs being developed. Preliminary results of these emerging agents that selectively target disease-defining pathogenic pathways seem to be promising, although long-term and large-scale studies assessing safety and efficacy are still lacking. The aim of this article was to review the clinical and research data of some emerging topical agents, focusing on Janus kinase-signal transducer and activator of transcription and phosphodiesterase type 4 inhibitors, which are currently being investigated.

  11. MpcAgent

    2013-11-29

    MpcAgent software is a module for the VolltronLite platform from PNNL that regulates the operation of rooftop air conditioning units in small to medium commercial buildings for the purpose of reducing peak power consumption. The MpcAgent accomplishes this by restricting the number of units that may operate simultaneously and using a model predictive control strategy to select which units to operate in each control period. The outcome of this control is effective control of themore » building air temperature at the user specified set point while avoiding expensive peak demand charges that result from running all HVAC units simultaneously.« less

  12. MpcAgent

    SciTech Connect

    Nutaro, James

    2013-11-29

    MpcAgent software is a module for the VolltronLite platform from PNNL that regulates the operation of rooftop air conditioning units in small to medium commercial buildings for the purpose of reducing peak power consumption. The MpcAgent accomplishes this by restricting the number of units that may operate simultaneously and using a model predictive control strategy to select which units to operate in each control period. The outcome of this control is effective control of the building air temperature at the user specified set point while avoiding expensive peak demand charges that result from running all HVAC units simultaneously.

  13. Radiation-Therapeutic Agent Clinical Trials: Leveraging Advantages of a National Cancer Institute Programmatic Collaboration.

    PubMed

    Takebe, Naoko; Ahmed, Mansoor M; Vikram, Bhadrasain; Bernhard, Eric J; Zwiebel, James; Norman Coleman, C; Kunos, Charles A

    2016-10-01

    A number of oncology phase II radiochemotherapy trials with promising results have been conducted late in the overall experimental therapeutic agent development process. Accelerated development and approval of experimental therapeutic agents have stimulated further interest in much earlier radiation-agent studies to increase the likelihood of success in phase III trials. To sustain this interest, more forward-thinking preclinical radiobiology experimental designs are needed to improve discovery of promising radiochemotherapy plus agent combinations for clinical trial testing. These experimental designs should better inform next-step radiation-agent clinical trial dose, schedule, exposure, and therapeutic effect. Recognizing the need for a better strategy to develop preclinical data supporting radiation-agent phase I or II trials, the National Cancer Institute (NCI)-Cancer Therapy Evaluation Program (CTEP) and the NCI-Molecular Radiation Therapeutics Branch of the Radiation Research Program have partnered to promote earlier radiobiology studies of CTEP portfolio agents. In this Seminars in Radiation Oncology article, four key components of this effort are discussed. First, we outline steps for accessing CTEP agents for preclinical testing. Second, we propose radiobiology studies that facilitate transition from preclinical testing to early phase trial activation. Third, we navigate steps that walk through CTEP agent strategic development paths available for radiation-agent testing. Fourth, we highlight a new NCI-sponsored cooperative agreement grant supporting in vitro and in vivo radiation-CTEP agent testing that informs early phase trial designs. Throughout the article, we include contemporary examples of successful radiation-agent development initiatives.

  14. Design, synthesis and evaluation of tacrine-flurbiprofen-nitrate trihybrids as novel anti-Alzheimer's disease agents.

    PubMed

    Chen, Yao; Sun, Jianfei; Huang, Zhangjian; Liao, Hong; Peng, Sixun; Lehmann, Jochen; Zhang, Yihua

    2013-05-01

    To search for multifunctional anti-Alzheimer's disease (AD) agents with good safety, the previously synthesized tacrine-flurbiprofen hybrids 1a and 1b were modified into tacrine-flurbiprofen-nitrate trihybrids 3a-h. These compounds displayed comparable or higher cholinesterase inhibitory activity relative to the bivalent hybrids. Compound 3a was the most potent, which released moderate NO, exerted blood vessel relaxative activity, and showed significant Aβ inhibitory effects whereas tacrine and flurbiprofen did not exhibit any Aβ inhibitory activity at the same dose. In addition, 3a was active in improving memory impairment in vivo. More importantly, the hepatotoxicity study showed that 3a was much safer than tacrine, suggesting it might be a promising anti-AD agent for further investigation.

  15. The antimicrobial properties of cedar leaf (Thuja plicata) oil; a safe and efficient decontamination agent for buildings.

    PubMed

    Hudson, James; Kuo, Michael; Vimalanathan, Selvarani

    2011-12-01

    Cedar leaf oil (CLO), derived from the Western red cedar, Thuja plicata, was evaluated as a safe and acceptable broad spectrum antimicrobial agent, with a view to its potential applications in buildings, including the alleviation of sick building syndrome. Various Gram-positive and Gram-negative human bacteria, and two fungal organisms, all known to be common environmental sources of potential infection, were selected and tested quantitatively, and all of them were found to be susceptible to CLO liquid and vapor. Bacterial spores and Aspergillus niger were sensitive, although less so than the vegetative bacteria. Similar tests with cultured human lung cells showed that continuous exposure to CLO vapor for at least 60 minutes was not toxic to the cells. Based on these results, CLO shows promise as a prospective safe, green, broad-spectrum anti-microbial agent for decontamination of buildings. PMID:22408584

  16. Agent Persuasion Mechanism of Acquaintance

    NASA Astrophysics Data System (ADS)

    Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

    Agent persuasion can improve negotiation efficiency in dynamic environment based on its initiative and autonomy, and etc., which is being affected much more by acquaintance. Classification of acquaintance on agent persuasion is illustrated, and the agent persuasion model of acquaintance is also illustrated. Then the concept of agent persuasion degree of acquaintance is given. Finally, relative interactive mechanism is elaborated.

  17. 13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. 108.1620 Section 108.1620 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM SBA...

  18. Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents.

    PubMed

    Meiyanto, Edy; Hermawan, Adam; Anindyajati

    2012-01-01

    Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction. Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product

  19. Scoping Planning Agents With Shared Models

    NASA Technical Reports Server (NTRS)

    Bedrax-Weiss, Tania; Frank, Jeremy D.; Jonsson, Ari K.; McGann, Conor

    2003-01-01

    In this paper we provide a formal framework to define the scope of planning agents based on a single declarative model. Having multiple agents sharing a single model provides numerous advantages that lead to reduced development costs and increase reliability of the system. We formally define planning in terms of extensions of an initial partial plan, and a set of flaws that make the plan unacceptable. A Flaw Filter (FF) allows us to identify those flaws relevant to an agent. Flaw filters motivate the Plan Identification Function (PIF), which specifies when an agent is is ready hand control to another agent for further work. PIFs define a set of plan extensions that can be generated from a model and a plan request. FFs and PIFs can be used to define the scope of agents without changing the model. We describe an implementation of PIFsand FFswithin the context of EUROPA, a constraint-based planning architecture, and show how it can be used to easily design many different agents.

  20. Battlefield agent collaboration

    NASA Astrophysics Data System (ADS)

    Budulas, Peter P.; Young, Stuart H.; Emmerman, Philip J.

    2001-09-01

    Small air and ground physical agents (robots) will be ubiquitous on the battlefield of the 21st century, principally to lower the exposure to harm of our ground forces in urban and open terrain scenarios. Teams of small collaborating physical agents conducting tasks such as Reconnaissance, Surveillance, and Target Acquisition (RSTA), intelligence, chemical and biological agent detection, logistics, decoy, sentry; and communications relay will have advanced sensors, communications, and mobility characteristics. It is anticipated that there will be many levels of individual and team collaboration between the soldier and robot, robot to robot, and robot to mother ship. This paper presents applications and infrastructure components that illustrate each of these levels. As an example, consider the application where a team of twenty small robots must rapidly explore and define a building complex. Local interactions and decisions require peer to peer collaboration. Global direction and information fusion warrant a central team control provided by a mother ship. The mother ship must effectively deliver/retrieve, service, and control these robots as well as fuse the information gathered by these highly mobile robot teams. Any level of collaboration requires robust communications, specifically a mobile ad hoc network. The application of fixed ground sensors and mobile robots is also included in this paper. This paper discusses on going research at the U.S. Army Research Laboratory that supports the development of multi-robot collaboration. This research includes battlefield visualization, intelligent software agents, adaptive communications, sensor and information fusion, and multi-modal human computer interaction.