Science.gov

Sample records for agents show promise

  1. Bacteriophages show promise as antimicrobial agents.

    PubMed

    Alisky, J; Iczkowski, K; Rapoport, A; Troitsky, N

    1998-01-01

    The emergence of antibiotic-resistant bacteria has prompted interest in alternatives to conventional drugs. One possible option is to use bacteriophages (phage) as antimicrobial agents. We have conducted a literature review of all Medline citations from 1966-1996 that dealt with the therapeutic use of phage. There were 27 papers from Poland, the Soviet Union, Britain and the U.S.A. The Polish and Soviets administered phage orally, topically or systemically to treat a wide variety of antibiotic-resistant pathogens in both adults and children. Infections included suppurative wound infections, gastroenteritis, sepsis, osteomyelitis, dermatitis, empyemas and pneumonia; pathogens included Staphylococcus, Streptococcus, Klebsiella, Escherichia, Proteus, Pseudomonas, Shigella and Salmonella spp. Overall, the Polish and Soviets reported success rates of 80-95% for phage therapy, with rare, reversible gastrointestinal or allergic side effects. However, efficacy of phage was determined almost exclusively by qualitative clinical assessment of patients, and details of dosages and clinical criteria were very sketchy. There were also six British reports describing controlled trials of phage in animal models (mice, guinea pigs and livestock), measuring survival rates and other objective criteria. All of the British studies raised phage against specific pathogens then used to create experimental infections. Demonstrable efficacy against Escherichia, Acinetobacter, Pseudomonas and Staphylococcus spp. was noted in these model systems. Two U.S. papers dealt with improving the bioavailability of phage. Phage is sequestered in the spleen and removed from circulation. This can be overcome by serial passage of phage through mice to isolate mutants that resist sequestration. In conclusion, bacteriophages may show promise for treating antibiotic resistant pathogens. To facilitate further progress, directions for future research are discussed and a directory of authors from the reviewed

  2. Experimental Drug for Rheumatoid Arthritis Shows Promise

    MedlinePlus

    ... news/fullstory_158076.html Experimental Drug for Rheumatoid Arthritis Shows Promise Baricitinib helped patients who failed other ... HealthDay News) -- An experimental drug to treat rheumatoid arthritis showed promise in a new six-month trial. ...

  3. Experimental Genital Herpes Drug Shows Promise

    MedlinePlus

    ... gov/medlineplus/news/fullstory_159462.html Experimental Genital Herpes Drug Shows Promise Drug lowered viral activity, recurrence ... News) -- An experimental immune-boosting treatment for genital herpes shows promise, researchers report. The drug, called GEN- ...

  4. Portable Zika Test Shows Promise in Monkeys

    MedlinePlus

    ... nih.gov/medlineplus/news/fullstory_158704.html Portable Zika Test Shows Promise in Monkeys Easy-to-use ... News) -- A fast, inexpensive test that detects the Zika virus in monkeys might be useful for doctors ...

  5. Portable Zika Test Shows Promise in Monkeys

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_158704.html Portable Zika Test Shows Promise in Monkeys Easy-to-use ... News) -- A fast, inexpensive test that detects the Zika virus in monkeys might be useful for doctors ...

  6. Malaria Vaccine Shows Promise in Small Study

    MedlinePlus

    ... nih.gov/medlineplus/news/fullstory_158765.html Malaria Vaccine Shows Promise in Small Study It protected more ... May 10, 2016 (HealthDay News) -- An experimental malaria vaccine protects a majority of adults against the mosquito- ...

  7. Malaria Vaccine Shows Promise in Small Study

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_158765.html Malaria Vaccine Shows Promise in Small Study It protected more ... May 10, 2016 (HealthDay News) -- An experimental malaria vaccine protects a majority of adults against the mosquito- ...

  8. Triazole: A Promising Antitubercular Agent.

    PubMed

    Keri, Rangappa S; Patil, Siddappa A; Budagumpi, Srinivasa; Nagaraja, Bhari Mallanna

    2015-10-01

    Tuberculosis is a contagious disease with comparatively high mortality worldwide. The statistics shows that around three million people throughout the world die annually from tuberculosis and there are around eight million new cases each year, of which developing countries showed major share. Therefore, the discovery and development of effective antituberculosis drugs with novel mechanism of action have become an insistent task for infectious diseases research programs. The literature reveals that, heterocyclic moieties have drawn attention of the chemists, pharmacologists, microbiologists, and other researchers owing to its indomitable biological potential as anti-infective agents. Among heterocyclic compounds, triazole (1,2,3-triazole/1,2,4-triazole) nucleus is one of the most important and well-known heterocycles, which is a common and integral feature of a variety of natural products and medicinal agents. Triazole core is considered as a privileged structure in medicinal chemistry and is widely used as 'parental' compounds to synthesize molecules with medical benefits, especially with infection-related activities. In the present review, we have collated published reports on this versatile core to provide an insight so that its complete therapeutic potential can be utilized for the treatment of tuberculosis. This review also explores triazole as a potential targeted core moiety against tuberculosis and various research ongoing worldwide. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic triazole-based antituberculosis drugs. PMID:25643871

  9. New Dengue Virus Vaccine Shows Promise

    MedlinePlus

    ... she stressed that more research, on a larger scale, will be needed to confirm the vaccine's promise. ... of Vermont College of Medicine, Burlington; Matthew Aliota, Ph.D., research scientist, department of pathobiological sciences, School ...

  10. Lightweight magnesium-lithium alloys show promise

    NASA Technical Reports Server (NTRS)

    Adams, W. T.; Cataldo, C. E.

    1964-01-01

    Evaluation tests show that magnesium-lithium alloys are lighter and more ductile than other magnesium alloys. They are being used for packaging, housings, containers, where light weight is more important than strength.

  11. Stem Cell Therapy Shows Promise Against Heart Failure

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158122.html Stem Cell Therapy Shows Promise Against Heart Failure A second ... 4, 2016 MONDAY, April 4, 2016 (HealthDay News) -- Stem cell therapy shows promise for people battling heart failure, ...

  12. Experimental Therapy Shows Promise for Type 1 Diabetes

    MedlinePlus

    ... Relief Health Capsules Experimental Therapy Shows Promise for Type 1 Diabetes Complementary Approaches for Depression Featured Website: Prescription Drug Abuse Past Issues Most Viewed June 2016 Print RSS ...

  13. New Drug Shows Promise for Rare Blood Cancers

    MedlinePlus

    ... nlm.nih.gov/medlineplus/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 ...

  14. 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 ...

  15. Gene Therapy Shows Early Promise Against Heart Failure

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158046.html Gene Therapy Shows Early Promise Against Heart Failure Inserting new ... who suffer from heart failure: A trial using gene therapy appears to have boosted patients' cardiac function. "This ...

  16. 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 ...

  17. 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 ...

  18. 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.

  19. 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.

  20. Spirooxindoles: Promising scaffolds for anticancer agents.

    PubMed

    Yu, Bin; Yu, De-Quan; Liu, Hong-Min

    2015-06-01

    The search for novel anticancer agents with more selectivity and lower toxicity continues to be an area of intensive investigation. The unique structural features of spirooxindoles together with diverse biological activities have made them privileged structures in new drug discovery. Among them, spiro-pyrrolidinyl oxindoles have been extensively studied as potent inhibitors of p53-MDM2 interaction, finally leading to the identification of MI-888, which could achieve rapid, complete and durable tumor regression in xenograft models of human cancer with oral administration and is in advanced preclinical research for cancer therapy. This review highlights recent progress of biologically active spirooxindoles for their anticancer potentials, mainly focusing on the discussions of SARs and modes of action. This article also aims to discuss potential further directions on the development of more potent analogues for cancer therapy. PMID:24994707

  1. Salt caverns show promise for nonhazardous oil field waste disposal

    SciTech Connect

    Veil, J.A.

    1996-11-18

    Salt caverns show promise for the disposal of non-hazardous oil field wastes, and there are no apparent regulatory barriers to this application. Solution-mined salt caverns have been used for many years for storing hydrocarbon products. Argonne National laboratory has reviewed the legality, technical suitability, and feasibility of disposing of nonhazardous oil and gas exploration and production wastes in salt caverns. An analysis of regulations indicates that there are no outright regulatory prohibitions on cavern disposal of oil field wastes at either the federal level or in the 11 oil-producing states that were studied (Kansas, Louisiana, Michigan, Mississippi, New Mexico, New York, North Dakota, Ohio, Oklahoma, Pennsylvania, and Texas). The paper discusses the two types of salt deposits in the US, regulatory concerns, wastes, cavern design, disposal operations, closure and remediation, and results of the feasibility study.

  2. Xenon fluorides show potential as fluorinating agents

    NASA Technical Reports Server (NTRS)

    Chernick, C. L.; Shieh, T. C.; Yang, N. C.

    1967-01-01

    Xenon fluorides permit the controlled addition of fluorine across an olefinic double bond. They provide a series of fluorinating agents that permit ready separation from the product at a high purity. The reactions may be carried out in the vapor phase.

  3. In-situ gasification and liquefaction show promise

    NASA Astrophysics Data System (ADS)

    Miskell, J. T.

    1980-05-01

    Recent progress in the development of in-situ coal gasification and shale liquefaction is discussed. The presence of potentially gasifiable subbituminous, bituminous and lignite coal reserves in the United States amounting to 1800 billion tons, compared with minable coal reserves of 430 billion tons, is pointed out as a major motivation for the development of in-situ extraction techniques, which are estimated to be some of the least expensive potential sources of synthetic natural gas. The successful test of an underground gasification unit operating for 35 days in a 23-ft thick coal seam dipping at 63 deg to produce low-Btu fuel gas and nitrogen-free synthesis gas that can be converted to hydrocarbons is presented, and operational, geological, environmental and economic constraints on the operation of such a unit are considered. In-situ extraction of kerogen from shale using conventional or RF methods is presented as the most promising means for utilizing the great reserves of shale in the United States, requiring little water and causing least disturbance to the environment, and it is noted that the RF process will probably become available by the mid-1980s.

  4. 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

  5. N-Cinnamoylated Aminoquinolines as Promising Antileishmanial Agents

    PubMed Central

    Vale-Costa, S.; Costa-Gouveia, J.; Pérez, B.; Silva, T.; Teixeira, C.; Gomes, P.

    2013-01-01

    A series of cinnamic acid conjugates of primaquine and chloroquine were evaluated for their in vitro antileishmanial activities. Although primaquine derivatives had modest activity, chloroquine conjugates exhibited potent activity against both promastigotes (50% inhibitory concentration [IC50] = 2.6 to 21.8 μM) and intramacrophagic amastigotes (IC50 = 1.2 to 9.3 μM) of Leishmania infantum. Both the high activity of these chloroquine analogues and their mild-to-low toxicity toward host cells make them promising leads for the discovery of new antileishmanial agents. PMID:23917315

  6. 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

  7. 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

  8. 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

  9. Promising oncolytic agents for metastatic breast cancer treatment

    PubMed Central

    Cody, James J; Hurst, Douglas R

    2015-01-01

    New therapies for metastatic breast cancer patients are urgently needed. The long-term survival rates remain unacceptably low for patients with recurrent disease or disseminated metastases. In addition, existing therapies often cause a variety of debilitating side effects that severely impact quality of life. Oncolytic viruses constitute a developing therapeutic modality in which interest continues to build due to their ability to spare normal tissue while selectively destroying tumor cells. A number of different viruses have been used to develop oncolytic agents for breast cancer, including herpes simplex virus, adenovirus, vaccinia virus, measles virus, reovirus, and others. In general, clinical trials for several cancers have demonstrated excellent safety records and evidence of efficacy. However, the impressive tumor responses often observed in preclinical studies have yet to be realized in the clinic. In order for the promise of oncolytic virotherapy to be fully realized for breast cancer patients, effectiveness must be demonstrated in metastatic disease. This review provides a summary of oncolytic virotherapy strategies being developed to target metastatic breast cancer.

  10. 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

  11. Chitosan and silver nanoparticles: promising anti-toxoplasma agents.

    PubMed

    Gaafar, M R; Mady, R F; Diab, R G; Shalaby, Th I

    2014-08-01

    Toxoplasmosis is a worldwide infection caused by obligate intracellular protozoan parasite which is Toxoplasma gondii. Chitosan and silver nanoparticles were synthesized to be evaluated singly or combined for their anti-toxoplasma effects as prophylaxis and as treatment in the experimental animals. Results were assessed through studying the parasite density and the ultrastructural parasite changes, and estimation of serum gamma interferon. Weight of tissue silver was assessed in different organs. Results showed that silver nanoparticles used singly or combined with chitosan have promising anti-toxoplasma potentials. The animals that received these compounds showed statistically significant decrease in the mean number of the parasite count in the liver and the spleen, when compared to the corresponding control group. Light microscopic examination of the peritoneal exudates of animals receiving these compounds showed stoppage of movement and deformity in shape of the tachyzoites, whereas, by scanning electron microscope, the organisms were mutilated. Moreover, gamma interferon was increased in the serum of animals receiving these compounds. All values of silver detected in different tissues were within the safe range. Thus, these nanoparticles proved their effectiveness against the experimental Toxoplasma infection. PMID:24852215

  12. 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

  13. 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

  14. 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. PMID:26200600

  15. One-a-Day Anti-Seizure Drug Shows Promise for People with Epilepsy

    MedlinePlus

    ... gov/medlineplus/news/fullstory_158318.html One-a-Day Anti-Seizure Drug Shows Promise for People With ... report. Their preliminary study compared the once-a-day drug eslicarbazepine acetate (Aptiom) to the twice-daily ...

  16. 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.

  17. 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

  18. NO-NSAIDs and cancer: promising novel agents.

    PubMed

    Rigas, B; Kalofonos, H; Lebovics, E; Vagenakis, A G

    2003-05-01

    Three potential applications of NO-donating NSAIDs in human cancer include their use: as chemopreventive agents; against already developed cancers (chemotherapy); and for the control of cancer symptoms, notably cancer pain. The evidence to date of greater safety and enhanced efficacy of NO-donating NSAIDs underscores their potential to prevent colon cancer and overcome the limitations of traditional NSAIDs. NO-donating NSAIDs affect several pathways critical to colon carcinogenesis and this may explain in part their greater efficacy in colon cancer prevention as assessed in preclinical models. PMID:12846441

  19. 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

  20. 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

  1. 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

  2. Reversible Cysteine Protease Inhibitors Show Promise for a Chagas Disease Cure

    PubMed Central

    Beaulieu, Christian; Black, W. Cameron; Isabel, Elise; Vasquez-Camargo, Fabio; Nath-Chowdhury, Milli; Massé, Frédéric; Mellon, Christophe; Methot, Nathalie

    2014-01-01

    The cysteine protease cruzipain is essential for the viability, infectivity, and virulence of Trypanosoma cruzi, the causative agent of Chagas disease. Thus, inhibitors of cruzipain are considered promising anti-T. cruzi chemotherapeutic agents. Reversible cruzipain inhibitors containing a nitrile “warhead” were prepared and demonstrated 50% inhibitory concentrations (IC50s) as potent as 1 nM in baculovirus-generated cruzipain enzyme assays. In epimastigote and intracellular amastigote in vitro assays, the most potent compounds demonstrated antiparasitic behavior in the 5 to 10 μM IC50 range; however, trypomastigote production from the amastigote form was ∼90 to 95% inhibited at 2 μM. Two key compounds, Cz007 and Cz008, with IC50s of 1.1 and 1.8 nM, respectively, against the recombinant enzyme were tested in a murine model of acute T. cruzi infection, with oral dosing in chow for 28 days at doses from 3 to 50 mg/kg of body weight. At 3 mg/kg of Cz007 and 3 mg/kg of Cz008, the blood parasitemia areas under the concentration-time curves were 16% and 25% of the untreated group, respectively. At sacrifice, 24 days after immunosuppression with cyclophosphamide, parasite presence in blood, heart, and esophagus was evaluated. Based on negative quantitative PCR results in all three tissues, cure rates in surviving animals were 90% for Cz007 at 3 mg/kg, 78% for Cz008 at 3 mg/kg, and 71% for benznidazole, the control compound, at 50 mg/kg. PMID:24323474

  3. Nature promises new anticancer agents: Interplay with the apoptosis-related BCL2 gene family.

    PubMed

    Christodoulou, Maria-Ioanna; Kontos, Christos K; Halabalaki, Maria; Skaltsounis, Alexios-Leandros; Scorilas, Andreas

    2014-03-01

    Natural products display special attributes in the treatment and prevention of a variety of human disorders including cancer. Their therapeutic capacities along with the fact that nature comprises a priceless pool of new compounds have attracted the interest of researchers worldwide. A significant number of organic compounds from terrestrial and marine organisms exhibit anticancer properties as attested by both in vitro and in vivo studies. Emerging evidence supporting the antineoplastic activity of natural compounds has rendered them promising agents in the fight against cancer. As a result, numerous natural compounds or their derivatives have entered clinical practice and are currently in the forefront of chemotherapeutics, showing beneficial effects for cancer patients. Induction of apoptosis seems to be the major mechanism of action induced by these natural agents in the race against cancer. This is mainly achieved through modulations of the expression of B-cell CLL/lymphoma 2 (BCL2) family members. These molecules appear to be the pivotal players determining cellular fate. In the current review, we provide a comprehensive overview of the major alterations in the gene and/or protein levels of BCL2-family members evoked in cancer cells after treatment with a gamut of natural compounds. The data cited suggest the need for exploitation of newly discovered natural products that, along with the improvement of currently employed chemotherapeutics, will significantly enrich the anticancer armamentarium. PMID:23848203

  4. ZnO Nanoparticles-Red Sandalwood Conjugate: A Promising Anti-Diabetic Agent.

    PubMed

    Kitture, Rohini; Chordiya, Kalyani; Gaware, Shankar; Ghosh, Sougata; More, Piyush A; Kulkarni, Parag; Chopade, Balu A; Kale, S N

    2015-06-01

    With the advances in nanoscience and nanotechnology the interest of researchers has expanded to interdisciplinary domain like bio-medical applications. Among such domains, one of the most important areas explored meticulously is the development of promising solutions in diabetes therapeutics. The disease associated with metabolic disorder, is one of the major challenges, due to its ever-increasing number of patients. The adverse effects of the synthetic enzymes like α-amylase and α-glucosidase inhibitors have invited many scientists to develop promising contender with minimal side-effects. On the other hand, Zinc has strong role in insulin synthesis, storage and secretion and thus its deficiency can be related to diabetes. In this context we have explored natural extract of Red Sandalwood (RSW) as a potent anti-diabetic agent, in conjugation with ZnO nanoparticles. ZnO nanoparticles have been synthesized via soft chemistry routes and duly characterized for their phase formation with the help of X-ray diffraction technique and Field-Emission Scanning Electron Microscopy. These monodispersed nanoparticles, -20 nm in size, were further conjugated to RSW extract. The conjugation chemistry was studied via Fourier transform infrared spectroscopy, UV-visible spectroscopy. Extract loading percentage was found from thermo-gravimetric analysis. 65% of the RSW extract was found conjugated to the ZnO nanoparticles. The anti-diabetic activity was assessed with the help of like α-amylase and α-glucosidase inhibition assay with murine pancreatic and small intestinal extracts. It was observed that the conjugated ZnO-RSW nanoparticles showed excellent activity against the crude murine pancreatic glucosidase as compared to the individual ZnO nanoparticles and the RSW extract. The ZnO-RSW conjugate showed 61.93% of inhibition while the bare ZnO nanoparticles and RSW showed 21.48% and 5.90% respectively. PMID:26369011

  5. Novel Drug Delivery System Shows Early Promise for Treating Lupus in Mice

    MedlinePlus

    ... effects, is a promising advance," concluded lead author Michael Look, Ph.D. This research was also supported ... Health Information | Research | Funding | News & Events | About Us | Portal en español | Asian-Language Publications Contact Us | Disclaimer | ...

  6. 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

  7. 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

  8. Preclinical evaluation of perifosine as a potential promising anti-rhabdomyosarcoma agent.

    PubMed

    Shen, Jie; Hong, Yue; Zhao, Qiong; Zhang, Jian-Li

    2016-01-01

    Rhabdomyosarcoma (RMS) is a highly malignant and metastatic pediatric cancer that arises from the skeletal muscle. Recent studies have identified an important role of AKT signaling in RMS progression. In the current study, we investigated the activity of perifosine, an oral alkylphospholipid AKT inhibitor, against human RMS cells (RD and Rh-30 lines) both in vivo and in vitro, and studied the underlying mechanisms. We showed that perifosine significantly inhibited RMS cell growth in concentration- and time-dependent manners. Meanwhile, perifosine induced dramatic apoptosis in RMS cells. At the signaling level, perifosine blocked AKT activation, while inducing reactive oxygen species (ROS) production as well as JNK and P38 phosphorylations in RMS cells. Restoring AKT activation by introducing a constitutively active-AKT (CA-AKT) only alleviated (not abolished) perifosine-induced cytotoxicity in RD cells. Yet, the ROS scavenger N-acetyl cysteine (NAC) as well as pharmacological inhibitors against JNK (SP-600125) or P38 (SB-203580) suppressed perifosine-induced cytotoxicity in RMS cells. Thus, perifosine induces growth inhibition and apoptosis in RMS cells through mechanisms more than just blocking AKT. In vivo, oral administration of perifosine significantly inhibited growth of Rh-30 xenografts in severe combined immunodeficient (SCID) mice. Our data indicate that perifosine might be further investigated as a promising anti-RMS agent. PMID:26269112

  9. KGB- agents (Part 2: Music and show -bussines)

    NASA Astrophysics Data System (ADS)

    Gaina, Alex

    2008-10-01

    The paper represents a continuation of the previous one 2008stuk.rept.....G and reffers to activity of KGB in the Show Busyness in the former USSR. During 1970-th the activity of KGB was concerned to control the market of musical disks, the disco clubs, the programs and the personal componence of the musical groups and orchestra.

  10. 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. PMID:23733982

  11. 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.

  12. 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

  13. 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…

  14. 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

  15. 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

  16. 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…

  17. Standard of Care and Promising New Agents for Triple Negative Metastatic Breast Cancer

    PubMed Central

    Mancini, Patrizia; Angeloni, Antonio; Risi, Emanuela; Orsi, Errico; Mezi, Silvia

    2014-01-01

    Triple negative breast cancer (TNBC) is a cluster of heterogeneous diseases, all of them sharing the lack of expression of estrogen and progesterone receptors and HER2 protein. They are characterized by different biological, molecular and clinical features, including a poor prognosis despite the increased sensitivity to the current cytotoxic therapies. Several studies have identified important molecular features which enable further subdivision of this type of tumor. We are drawing from genomics, transcription and translation analysis at different levels, to improve our knowledge of the molecular alterations along the pathways which are activated during carcinogenesis and tumor progression. How this information should be used for the rational selection of therapy is an ongoing challenge and the subject of numerous research studies in progress. Currently, the vascular endothelial growth factor (VEGF), poly (ADP-ribose) polymerase (PARP), HSP90 and Aurora inhibitors are most used as targeting agents in metastatic setting clinical trials. In this paper we will review the current knowledge about the genetic subtypes of TNBC and their different responses to conventional therapeutic strategies, as well as to some new promising molecular target agents, aimed to achieve more tailored therapies. PMID:25347122

  18. Promises, Promises.

    PubMed

    McLean, Haydn

    2016-03-01

    Presenting a pledge to another establishes expectation in the recipient for the commitment to be fulfilled, particularly when a promise is devoid of coercion. Defaulting on a commitment may damage relationships between people and may predispose the disenchanted recipient to distrust those who proffer succeeding commitments. God's advocates who have been disappointed by God's evident under-delivery may experience a crisis of faith, exemplified in attachment distress, when disappointment intimates God has over-promised his providence, which questions the nature and, ultimately, the relevance of God. PMID:26956758

  19. 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.

  20. 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

  1. 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

  2. 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

  3. New oxidovanadium(IV) N-acylhydrazone complexes: promising antileishmanial and antitrypanosomal agents.

    PubMed

    Benítez, Julio; Cavalcanti de Queiroz, Aline; Correia, Isabel; Alves, Marina Amaral; Alexandre-Moreira, Magna S; Barreiro, Eliezer J; Lima, Lidia Moreira; Varela, Javier; González, Mercedes; Cerecetto, Hugo; Moreno, Virtudes; Pessoa, João Costa; Gambino, Dinorah

    2013-04-01

    Searching for new promising metal-based hits against Trypanosoma cruzi and Leishmania parasites, two related oxidovanadium(IV) N-acylhydrazone complexes, [V(IV)O(LASSBio1064-2H)(H2O)], 1, and [V(IV)O(LASSBio1064-2H)(phen)]·(H2O), 2, where LASSBio1064=(E)-N'-(2-hydroxybenzylidene-4-chlorobenzohydrazide and phen = 1,10-phenanthroline, were synthesized and characterized in the solid state and in solution by elemental analysis, conductimetric measurements and ESI-MS, FTIR, EPR and (51)V NMR spectroscopies and were evaluated on T. cruzi and Leishmania major. In addition, their unspecific cytotoxicity was tested against murine macrophages. Furthermore, to provide insight into the possible mechanism of its antiparasitic action, [VO(LASSbio1064-2H)(phen)].(H2O) was tested for its DNA interaction ability on plasmid DNA by atomic force microscopy (AFM) and on CT DNA by using DNA viscosity measurements and fluorescence spectroscopy. Both complexes were active in vitro against the epimastigote form of T. cruzi (Tulahuen 2 strain) showing IC50 values of the same order or significantly lower than that of the reference trypanosomicidal drug Nifurtimox. However, only the mixed-ligand oxidovanadium(IV) complex 2, which includes phen in its coordination sphere, showed activity on L. major promastigotes with a IC50 value of 22.1 ± 0.6 μM. The compounds show low toxicity on mammalian cells (IC50 > 100 μM). DNA interaction studies showed that the mixed-ligand complex is able to interact with this biomolecule probably through an intercalative mode, pointing out at DNA as a potential target in the parasite. The results suggest that [V(IV)O(LASSBio1064-2H)(phen)]·(H2O) may be a promising compound for further drug development stages. PMID:23353731

  4. 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

  5. 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

  6. Chiral copper(II) complex based on natural product rosin derivative as promising antitumour agent.

    PubMed

    Fei, Bao-Li; Huang, Zhi-Xiang; Xu, Wu-Shuang; Li, Dong-Dong; Lu, Yang; Gao, Wei-Lin; Zhao, Yue; Zhang, Yu; Liu, Qing-Bo

    2016-07-01

    To evaluate the biological preference of chiral drug candidates for molecular target DNA, the synthesis and characterization of a chiral copper(II) complex (2) of a chiral ligand N,N'-(pyridin-2-ylmethylene) dehydroabietylamine (1) was carried out. The interactions of 1 and 2 with salmon sperm DNA were investigated by viscosity measurements, UV, fluorescence and circular dichroism (CD) spectroscopic techniques. Absorption spectral, emission spectral and viscosity analysis reveal that 1 and 2 interacted with DNA through intercalation and 2 exhibited a higher DNA binding ability. In the absence/presence of ascorbic acid, 1 and 2 cleaved supercoiled pBR322 DNA by single-strand and 2 displayed stronger DNA cleavage ability. In addition, in vitro cytotoxicity of 1 and 2 against HeLa, SiHa, HepG-2 and A431 cancer cell lines study show that they exhibited effective cytotoxicity against the tested cell lines, notably, 2 showed a superior cytotoxicity than the widely used drug cisplatin under identical conditions, indicating it has the potential to act as effective anticancer drug. Flow cytometry analysis indicates 2 produced death of HeLa cancer cells through an apoptotic pathway. Cell cycle analysis demonstrates that 2 mainly arrested HeLa cells at the S phase. The study represents the first step towards understanding the mode of the promising chiral rosin-derivative based copper complexes as chemotherapeutics. PMID:27088508

  7. 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

  8. 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

  9. Draft Whole-Genome Sequence of Trichoderma gamsii T6085, a Promising Biocontrol Agent of Fusarium Head Blight on Wheat.

    PubMed

    Baroncelli, Riccardo; Zapparata, Antonio; Piaggeschi, Giulia; Sarrocco, Sabrina; Vannacci, Giovanni

    2016-01-01

    Trichoderma gamsii T6085 is a promising beneficial isolate whose effects consist of growth inhibition of the main agents causing Fusarium head blight, reduction of mycotoxin accumulation, competition for wheat debris, and reduction of the disease in both the lab and the field. Here, we present the first genome assembly of a T. gamsii isolate, providing a useful platform for the scientific community. PMID:26893428

  10. Draft Whole-Genome Sequence of Trichoderma gamsii T6085, a Promising Biocontrol Agent of Fusarium Head Blight on Wheat

    PubMed Central

    Baroncelli, Riccardo; Zapparata, Antonio; Piaggeschi, Giulia; Vannacci, Giovanni

    2016-01-01

    Trichoderma gamsii T6085 is a promising beneficial isolate whose effects consist of growth inhibition of the main agents causing Fusarium head blight, reduction of mycotoxin accumulation, competition for wheat debris, and reduction of the disease in both the lab and the field. Here, we present the first genome assembly of a T. gamsii isolate, providing a useful platform for the scientific community. PMID:26893428

  11. 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

  12. 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

  13. 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

  14. 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

  15. Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents.

    PubMed

    Hampannavar, Girish A; Karpoormath, Rajshekhar; Palkar, Mahesh B; Shaikh, Mahamadhanif S; Chandrasekaran, Balakumar

    2016-07-14

    Series of styryl hydrazine thiazole hybrids inspired from dehydrozingerone (DZG) scaffold were designed and synthesized by molecular hybridization approach. In vitro antimycobacterial activity of synthesized compounds was evaluated against Mycobacterium tuberculosis H37Rv strain. Among the series, compound 6o exhibited significant activity (MIC = 1.5 μM; IC50 = 0.48 μM) along with bactericidal (MBC = 12 μM) and intracellular antimycobacterial activities (IC50 = <0.098 μM). Furthermore, 6o displayed prominent antimycobacterial activity under hypoxic (MIC = 46 μM) and normal oxygen (MIC = 0.28 μM) conditions along with antimycobacterial efficiency against isoniazid (MIC = 3.2 μM for INH-R1; 1.5 μM for INH-R2) and rifampicin (MIC = 2.2 μM for RIF-R1; 6.3 μM for RIF-R2) resistant strains of Mtb. Presence of electron donating groups on the phenyl ring of thiazole moiety had positive correlation for biological activity, suggesting the importance of molecular hybridization approach for the development of newer DZG clubbed hydrazine thiazole hybrids as potential antimycobacterial agents. PMID:27437078

  16. Glutathione as a promising anti-hydrophobicity agent against Malassezia spp.

    PubMed

    Sivasankar, Chandran; Ponmalar, Ayyappan; Bhaskar, James P; Pandian, Shunmugiah K

    2015-10-01

    The genus Malassezia has recently attracted wide attention in medical microbiology and dermatology as a pathogen. They are lipophilic yeasts possessing high level of cell surface hydrophobicity (CSH). L-glutathione (GSH) is a ubiquitous antioxidant which offers protection against microbial infections. This study is intended to investigate the role of GSH as a potential anti-hydrophobicity agent against Malazessia spp. Microbial adherence to hydrocarbon assay was performed to assess the anti-hydrophobicity activity (AHA) of GSH against four Malassezia spp. The assay revealed that GSH at 400 μg ml(-1) concentration inhibited CSH, ranging from 84% to 95% in M. furfur, M. globosa, M. restricta and M. sympodialis without killing the cells. The AHA of GSH was corroborated by auto-aggregation assay and zeta-potential measurement, through which delayed cell aggregation was observed due to reduction in CSH level and not by modification in cell surface charge. In addition, colony-forming unit assay was performed in which 62-93% of CSH reduction was observed in Malassezia spp. tested. Furthermore, GSH treatment enhanced the sensitivity of Malassezia spp. towards human blood at the rate of 64-72%. The AHA was further confirmed through Fourier transform infrared analysis. Thus, this study portrays GSH as a prospective therapeutic alternative for Malassezia-mediated infections. PMID:26334025

  17. 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.

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

    PubMed

    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. PMID:26714861

  19. Denosumab as a promising novel bone-targeted agent in castration resistant prostate cancer.

    PubMed

    Dellis, Athanasios; Papatsoris, Athanasios G

    2014-01-01

    Fortunately, more therapeutic progress has been achieved during the last 3 years for patients with castration resistant prostate cancer (CRPC) than during the previous 30 years. During this limited time frame, six compounds (sipuleucel-T, cabazitaxel, denosumab, abiraterone, radium-223 and enzalutamide, listed in chronologic order) yielded positive results in Phase III trials (Fizazi K. Nonhormone therapy for metastatic castration-resistant prostate cancer. Soc Clin Oncol Educ Book 2013;2013:161-5; Papatsoris AG, Karamouzis MV, Papavassiliou AG. Novel biological agents for the treatment of hormone-refractory prostate cancer (HRPC). Curr Med Chem 2005;12(3):277-96). Regarding skeletal related event (SREs) in patients with CRPC the last 20 years bisphosphonates (i.e., zolendronic acid) were the standard of care until the development of denosumab, which is a novel receptor-activated nuclear factor kappa-β ligand inhibitor. Recent studies demonstrated that denosumab (subcutaneous use) was better than zolendronic acid (intravenous use) for the prevention of SREs and the increase of the bone-metastasis-free survival, while the rate and grade of adverse effects was similar, except for osteonecrosis of the jaw and hypocalcemia. Cost-effectiveness of denosumab is under review in ongoing comparative studies. PMID:24074253

  20. Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies

    PubMed Central

    Gaudio, Carlo; Greco, Cesare; Keylani, Abdul M.; D'Agostino, Darrin C.

    2014-01-01

    This systematic review aims to provide an update on pharmacological and interventional strategies for the treatment of pulmonary arterial hypertension in adults. Currently US Food and Drug Administration approved drugs including prostanoids, endothelin-receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate-cyclase stimulators. These agents have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance ten years ago to delayed disease progression today. On the other hand, percutaneous balloon atrioseptostomy by using radiofrequency perforation, cutting balloon dilatation, or insertion of butterfly stents and pulmonary artery catheter-based denervation, both associated with very low rate of major complications and death, should be considered in combination with specific drugs at an earlier stage rather than late in the progression of pulmonary arterial hypertension and before the occurrence of overt right-sided heart failure. PMID:25013799

  1. 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

  2. A modified HSP70 inhibitor shows broad activity as an anticancer agent

    PubMed Central

    Balaburski, Gregor M.; Leu, Julia I-Ju; Beeharry, Neil; Hayik, Seth; Andrake, Mark D.; Zhang, Gao; Herlyn, Meenhard; Villanueva, Jessie; Dunbrack, Roland L.; Yen, Tim; George, Donna L.; Murphy, Maureen E.

    2013-01-01

    The stress-induced heat shock protein 70 (HSP70) is an ATP-dependent molecular chaperone that plays a key role in refolding misfolded proteins and promoting cell survival following stress. HSP70 is marginally expressed in non-transformed cells, but is greatly overexpressed in tumor cells. Silencing HSP70 is uniformly cytotoxic to tumor but not normal cells; therefore, there has been great interest in the development of HSP70 inhibitors for cancer therapy. Here we report that the HSP70 inhibitor 2-phenylethynesulfonamide (PES) binds to the substrate-binding domain of HSP70, and requires the C-terminal helical ‘lid’ of this protein (amino acids 573-616) in order to bind. Using molecular modeling and in silico docking, we have identified a candidate binding site for PES in this region of HSP70, and we identify point mutants that fail to interact with PES. A preliminary structure-activity relationship analysis has revealed a derivative of PES, 2-(3-chlorophenyl) ethynesulfonamide (PES-Cl), which shows increased cytotoxicity and ability to inhibit autophagy, along with significantly improved ability to extend the life of mice with pre-B cell lymphoma, compared to the parent compound (p=0.015). Interestingly, we also show that these HSP70 inhibitors impair the activity of the Anaphase Promoting Complex/Cyclosome (APC/C) in cell-free extracts, and induce G2/M arrest and genomic instability in cancer cells. PES-Cl is thus a promising new anti-cancer compound with several notable mechanisms of action. PMID:23303345

  3. 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

  4. 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

  5. Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease

    PubMed Central

    Essone, Paulin N.; Chegou, Novel N.; Loxton, Andre G.; Stanley, Kim; Kriel, Magdalena; van der Spuy, Gian; Franken, Kees L.; Ottenhoff, Tom H.; Walzl, Gerhard

    2014-01-01

    Background We previously identified Mycobacterium tuberculosis (M.tb) antigen-induced host markers that showed promise as TB diagnostic candidates in 7-day whole blood culture supernatants. The aim of the present study was to evaluate the utility of these markers further, and cross-compare results with short-term antigen stimulated and unstimulated culture supernatants. Methods We recruited 15 culture confirmed TB cases and 15 non-TB cases from a high-TB endemic community in Cape Town, South Africa into a pilot case-control study from an on-going larger study. Blood samples collected from study participants were stimulated with 4 M.tb antigens that were previously identified as promising (ESAT6/CFP10 (early secreted), Rv2029c (latency), Rv2032 (latency) and Rv2389c (rpf)) in a 7-day or overnight culture assay. Supernatants were also collected form the standard QuantiFERON In Tube (QFT-IT) test. The levels of 26 host markers were evaluated in the three culture supernatants using the Luminex platform. Results The unstimulated levels of CRP, Serum amyloid P (SAP) and serum amyloid A (SAA) and ESAT-6/CFP-10 specific IP-10 and SAA were amongst the best discriminatory markers in all 3 assays, ascertaining TB with AUC of 72–84%. Four-marker models accurately classified up to 92%, 100% and 100% of study participants in the overnight, 7-day and Quantiferon culture supernatants, respectively, after leave-one-out cross validation. Conclusion Unstimulated and antigen-specific levels of CRP, SAA, IP-10, MMP-2 and sCD40L hold promise as diagnostic candidates for TB disease in short-term stimulation assays. Larger studies are required to validate these findings but the data suggest that antigen-specific cytokine production and in particular mutimarker biosignatures might contribute to future diagnostic strategies. PMID:25025278

  6. 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

  7. Bezafibrate and medroxyprogesterone acetate target resting and CD40L-stimulated primary marginal zone lymphoma and show promise in indolent B-cell non-Hodgkin lymphomas.

    PubMed

    Hayden, Rachel E; Kussaibati, Racha; Cronin, Laura M; Pratt, Guy; Roberts, Claudia; Drayson, Mark T; Bunce, Christopher M

    2015-04-01

    B cell non-Hodgkin lymphomas (B-NHLs) are the most common adult hematological cancers and many remain incurable. Development of chemotherapy regimens is confounded by the prevalence of B-NHL in older, frailer patients and the chemo-protective tumor microenvironment. Although biological therapies such as rituximab have significantly improved outcomes and selective kinase inhibitors are showing promise, the rate of new drug discovery remains disappointing, the treatments expensive and long-term benefits uncertain. An alternative strategy is redeployment of available, inexpensive and non-toxic drugs. Here, we demonstrate the antiproliferative and mitochondrial superoxide (MSO) driven pro-apoptotic activities of bezafibrate (BEZ) and medroxyprogesterone acetate (MPA) against B-NHL cells, with a bias toward MZL, in the presence and absence of the microenvironmental signal CD40L. Our study is the first to confirm the presence of CD40L within the lymph node of B-NHL and its capacity to drive B-NHL proliferation. These findings implicate BEZ + MPA as a potential therapeutic strategy in B-NHL. PMID:24996440

  8. 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

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

    PubMed

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

    2016-01-26

    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

  10. 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

  11. Growth inhibition of Mycobacterium smegmatis by prodrugs of deoxyxylulose phosphate reducto-isomerase inhibitors, promising anti-mycobacterial agents.

    PubMed

    Ponaire, Sarah; Zinglé, Catherine; Tritsch, Denis; Grosdemange-Billiard, Catherine; Rohmer, Michel

    2012-05-01

    Since Mycobacterium tuberculosis sets up several multiple anti-tuberculosis drug resistance mechanisms, development of new drugs with innovative target is urgent. The methylerythritol phosphate pathway (MEP) involved in the biosynthesis of essential metabolites for the survival of mycobacteria, represents such a target. Fosmidomycin 1a and FR900098 1b, two inhibitors of DXR, do not affect the viability of M. tuberculosis cells, due to a lack of uptake. To overcome the absence of the mycobacterial cell wall crossing of these compounds, we synthesized and tested the inhibition potency of acyloxymethyl phosphonate esters as prodrugs of fosmidomycin 1a, FR900098 1b and their analogs 2a and 2b on Mycobacterium smegmatis. Only the prodrugs 4b-6b inhibit the bacterial growth and could be effective anti-mycobacterial agents. PMID:22405649

  12. 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. PMID:26807857

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

    PubMed Central

    Sharma, Monika; Tuaine, Jo; McLaren, Blair; Waters, Debra L.; Black, Katherine

    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. PMID:26807857

  14. Poor oral bioavailability of a promising anticancer agent andrographolide is due to extensive metabolism and efflux by P-glycoprotein.

    PubMed

    Ye, Ling; Wang, Tao; Tang, Lan; Liu, Wei; Yang, Zhen; Zhou, Juan; Zheng, Zhijie; Cai, Zheng; Hu, Ming; Liu, Zhongqiu

    2011-11-01

    Andrographolide (AP), isolated from Andrographis paniculata (Burm. F.) Nees, is an anticancer agent with significant clinical potential. This study determined its oral bioavailability and how intestinal disposition affects its bioavailability. Pharmacokinetics was evaluated in rats. Intestinal disposition was determined using a single-pass rat intestinal perfusion model and the cultured Caco-2 cells and Madin-Darby canine kidney II cells over expressing human P-gp (MDR1-MDCKII). Absolute bioavailability of AP was 2.67%. In the duodenum and jejunum, AP was rapidly metabolized to a sulfonate, identified as 14-deoxy-12-sulfo- andrographolide. AP was also rapidly metabolized by liver S9 fraction and in blank perfusates collected from duodenum and jejunum. The apparent permeability (P(app) ) of AP from basolateral (B) to apical (A) (4.94 × 10 cm/s) in the Caco-2 model was four times higher than the P(app) from A to B (1.14 × 10(-5) cm/s). Moreover, AP was significantly more permeable in the B to A direction than the opposite direction in MDR1-MDCKII cells. In the perfusion model, the effective permeability (P*(eff) ) for AP was highest in the duodenum, followed by jejunum, and then ileum and colon. In the ileum and colon, the P*(eff) for AP was significantly increased by verapamil, a P-glycoprotein (P-gp) inhibitor. AP has poor oral bioavailability because of its rapid biotransformation and efflux by P-gp. PMID:21721007

  15. 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

  16. Endophytic Bacillus subtilis Strain E1R-J Is a Promising Biocontrol Agent for Wheat Powdery Mildew

    PubMed Central

    Gong, Yufei; Huo, Yunxia; Han, Qingmei; Kang, Zhensheng; Huang, Lili

    2015-01-01

    In this study, the biocontrol efficacies of 14 endophytic bacterial strains were tested against Blumeria graminis f. sp. tritici (Bgt) in pot experiments under greenhouse conditions. Bacillus subtilis strain E1R-j significantly reduced disease index and exhibited the best control (90.97%). When different formulations of E1R-j were sprayed 24 h before Bgt inoculation, fermentation liquid without bacterial cell and crude protein suspension displayed the similar effects; and they reduced disease index more than bacterial cell suspension (109 cfu mL−1) and fermentation liquid without protein. The control effects were not significantly different between 1011 and 109 cfu mL−1 of bacterial cell suspension but were higher than 107 cfu mL−1. Further observations showed that conidial germination and appressorial formation of Bgt were retarded by spraying E1R-j 24 h before Bgt inoculation. Compared with the water check, conidial germination and appressorial formation were decreased by 43.3% and 42.7%, respectively. In the treatment with E1R-j, the number of houstoria significantly reduced and the speed of mycelial extension was slowed down in the wheat leaves. Scanning electron microscopy observation revealed that E1R-j significantly suppressed the conidial germination and caused rupture and deformation of germ tubes. On the surface of wheat leaves, mycelia and conidiophores became shrinking. PMID:25759819

  17. 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

  18. Naturally occurring sulfonium-ion glucosidase inhibitors and their derivatives: a promising class of potential antidiabetic agents.

    PubMed

    Mohan, Sankar; Eskandari, Razieh; Pinto, B Mario

    2014-01-21

    In humans, four different enzymes mediate the digestion of ingested carbohydrates. First salivary and pancreatic α-amylases, the two endoacting retaining glucosidases, break down the complex starch molecules into smaller linear maltose-oligomers (LM) and branched α-limit dextrins (αLDx). Then two retaining exoglucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI), convert those molecules into glucose in the small intestine. The small intestinal brush-border epithelial cells anchor MGAM and SI, and each contains a catalytic N- and C-terminal subunit, ntMGAM, ctMGAM, ntSI, and ctSI, respectively. All four catalytic domains have, to varying extents, α-1,4-exohydrolytic glucosidase activity and belong to the glycoside hydrolase family 31 (GH31). ntSI and ctSI show additional activity toward α-1,6 (isomaltose substrates) and α-1,2 (sucrose) glycosidic linkages, respectively. Because they mediate the final steps of starch digestion, both MGAM and SI are important target enzymes for the treatment of type-2 diabetes. Because of their potent inhibitory activities against the mammalian intestinal α-glucosidases, sulfonium-ion glucosidase inhibitors isolated from the antidiabetic herbal extracts of various Salacia species have received considerable attention recently. Thus far, researchers have isolated eight sulfonium-ion glucosidase inhibitors from Salacia species: salaprinol, salacinol, ponkoranol, kotalanol, and four of their corresponding de-O-sulfonated compounds, the structures of which comprise a 1,4-anhydro-4-thio-d-arabinitol and a polyhydroxylated acyclic side chain. Some of these compounds more strongly inhibit human intestinal α-glucosidases than the currently available antidiabetic drugs, acarbose and miglitol, and could serve as lead candidates in the treatment of type-2 diabetes. In this Account, we summarize progress in the field since 2010 with this class of inhibitors, with particular focus on their selective inhibitory activities

  19. 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. PMID:25589204

  20. 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,…

  1. An Amphipathic Undecapeptide with All d-Amino Acids Shows Promising Activity against Colistin-Resistant Strains of Acinetobacter baumannii and a Dual Mode of Action.

    PubMed

    Oddo, Alberto; Thomsen, Thomas T; Kjelstrup, Susanne; Gorey, Ciara; Franzyk, Henrik; Frimodt-Møller, Niels; Løbner-Olesen, Anders; Hansen, Paul R

    2016-01-01

    Multiple strains of Acinetobacter baumannii have developed multidrug resistance (MDR), leaving colistin as the only effective treatment. The cecropin-α-melittin hybrid BP100 (KKLFKKILKYL-NH2) and its analogs have previously shown activity against a wide array of plant and human pathogens. In this study, we investigated the in vitro antibacterial activities of 18 BP100 analogs (four known and 14 new) against the MDR A. baumannii strain ATCC BAA-1605, as well as against a number of other clinically relevant human pathogens. Selected peptides were further evaluated against strains of A. baumannii that acquired resistance to colistin due to mutations of the lpxC, lpxD, pmrA, and pmrB genes. The novel analogue BP214 showed antimicrobial activity at 1 to 2 μM and a hemolytic 50% effective concentration (EC50) of >150 μM. The lower activity of its enantiomer suggests a dual, specific and nonspecific mode of action. Interestingly, colistin behaved antagonistically to BP214 when pmrAB and lpxC mutants were challenged. PMID:26574005

  2. 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

  3. 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.

  4. 55P0110, a Novel Synthetic Compound Developed from a Plant Derived Backbone Structure, Shows Promising Anti-Hyperglycaemic Activity in Mice.

    PubMed

    Brunmair, Barbara; Lehner, Zsuzsanna; Stadlbauer, Karin; Adorjan, Immanuel; Frobel, Klaus; Scherer, Thomas; Luger, Anton; Bauer, Leonhardt; Fürnsinn, Clemens

    2015-01-01

    Starting off with a structure derived from the natural compound multiflorine, a derivatisation program aimed at the discovery and initial characterisation of novel compounds with antidiabetic potential. Design and discovery of the structures was guided by oral bioactivities obtained in oral glucose tolerance tests in mice. 55P0110, one among several new compounds with distinct anti-hyperglycaemic activity, was further examined to characterise its pharmacology and mode of action. Whereas a single oral dose of 55P0110 did not affect basal glycaemia, it markedly improved the glucose tolerance of healthy and diabetic mice (peak blood glucose in glucose tolerance test, mmol/l: healthy mice with 90 mg/kg 55P0110, 17.0 ± 1.2 vs. 10.1 ± 1.1; diabetic mice with 180 mg/kg 55P0110, 23.1 ± 0.9 vs. 11.1 ± 1.4; p<0.001 each). Closer examination argued against retarded glucose resorption from the gut, increased glucose excretion in urine, acute insulin-like or insulin sensitising properties, and direct inhibition of dipeptidyl peptidase-4 as the cause of glucose lowering. Hence, 55P0110 seems to act via a target not exploited by any drug presently approved for the treatment of diabetes mellitus. Whereas the insulinotropic sulfonylurea gliclazide (16 mg/kg) distinctly increased the circulating insulin-per-glucose ratio under basal conditions, 55P0110 (90 mg/kg) lacked such an effect (30 min. after dosing, nmol/mol: vehicle, 2.49 ± 0.27; 55P0110, 2.99 ± 0.35; gliclazide, 8.97 ± 0.49; p<0.001 each vs. gliclazide). Under an exogenous glucose challenge, however, 55P0110 increased this ratio to the same extent as gliclazide (20 min. after glucose feeding: vehicle, 2.53 ± 0.41; 55P0110, 3.80 ± 0.46; gliclazide, 3.99 ± 0.26; p<0.05 each vs. vehicle). By augmenting the glucose stimulated increase in plasma insulin, 55P0110 thus shows distinct anti-hyperglycaemic action in combination with low risk for fasting hypoglycaemia in mice. In summary, we have discovered a novel class of

  5. 55P0110, a Novel Synthetic Compound Developed from a Plant Derived Backbone Structure, Shows Promising Anti-Hyperglycaemic Activity in Mice

    PubMed Central

    Brunmair, Barbara; Lehner, Zsuzsanna; Stadlbauer, Karin; Adorjan, Immanuel; Frobel, Klaus; Scherer, Thomas; Luger, Anton; Bauer, Leonhardt; Fürnsinn, Clemens

    2015-01-01

    Starting off with a structure derived from the natural compound multiflorine, a derivatisation program aimed at the discovery and initial characterisation of novel compounds with antidiabetic potential. Design and discovery of the structures was guided by oral bioactivities obtained in oral glucose tolerance tests in mice. 55P0110, one among several new compounds with distinct anti-hyperglycaemic activity, was further examined to characterise its pharmacology and mode of action. Whereas a single oral dose of 55P0110 did not affect basal glycaemia, it markedly improved the glucose tolerance of healthy and diabetic mice (peak blood glucose in glucose tolerance test, mmol/l: healthy mice with 90 mg/kg 55P0110, 17.0±1.2 vs. 10.1±1.1; diabetic mice with 180 mg/kg 55P0110, 23.1±0.9 vs. 11.1±1.4; p<0.001 each). Closer examination argued against retarded glucose resorption from the gut, increased glucose excretion in urine, acute insulin-like or insulin sensitising properties, and direct inhibition of dipeptidyl peptidase-4 as the cause of glucose lowering. Hence, 55P0110 seems to act via a target not exploited by any drug presently approved for the treatment of diabetes mellitus. Whereas the insulinotropic sulfonylurea gliclazide (16 mg/kg) distinctly increased the circulating insulin-per-glucose ratio under basal conditions, 55P0110 (90 mg/kg) lacked such an effect (30 min. after dosing, nmol/mol: vehicle, 2.49±0.27; 55P0110, 2.99±0.35; gliclazide, 8.97±0.49; p<0.001 each vs. gliclazide). Under an exogenous glucose challenge, however, 55P0110 increased this ratio to the same extent as gliclazide (20 min. after glucose feeding: vehicle, 2.53±0.41; 55P0110, 3.80±0.46; gliclazide, 3.99±0.26; p<0.05 each vs. vehicle). By augmenting the glucose stimulated increase in plasma insulin, 55P0110 thus shows distinct anti-hyperglycaemic action in combination with low risk for fasting hypoglycaemia in mice. In summary, we have discovered a novel class of fully synthetic

  6. Endoxifen shows promise in breast cancer.

    PubMed

    2014-02-01

    In a phase I trial of endoxifen, a metabolite of tamoxifen, multiple patients with estrogen receptor-positive breast cancer that was resistant to treatment with aromatase inhibitors had partial responses or long-lasting stable disease. PMID:24501306

  7. 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) ...

  8. "First Things First" Shows Promising Results

    ERIC Educational Resources Information Center

    Hendrie, Caroline

    2005-01-01

    In this article, the author discusses a school improvement model, First Things First, developed by James P. Connell, a former tenured professor of psychology at the University of Rochester in New York. The model has three pillars for the high school level: (1) small, themed learning communities that each keep a group of students together…

  9. 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...

  10. 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

  11. Synthesis of novel triazole/isoxazole functionalized 7-(trifluoromethyl)pyrido[2,3-d]pyrimidine derivatives as promising anticancer and antibacterial agents.

    PubMed

    Naresh Kumar, R; Jitender Dev, G; Ravikumar, N; Krishna Swaroop, D; Debanjan, B; Bharath, G; Narsaiah, B; Nishant Jain, S; Gangagni Rao, A

    2016-06-15

    A series of novel 1,2,3-triazole/isoxazole functionalized pyrido[2,3-d]pyrimidine derivatives 6a-c, 7a-h and 8a-e were prepared in series of synthetic steps. All the compounds screened for the anticancer activity against four human cancer cell lines using Nocodazole as standard. Compounds 7d and 7h showed highest activity against PANC-1 (pancreatic cancer) and A549 (lung cancer) cell lines respectively and more than standard. All the compounds also screened for antibacterial activity using Rifampicin and Ciprofloxacin as standards and identified promising compounds further evaluated for minimum inhibitory concentration to validate the data. PMID:27130357

  12. 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.

  13. 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

  14. 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

  15. 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

  16. Population establishment of and promising early results with the brown lygodium moth, Neomusotima conspurcatalis - a candidate biological control agent of Old World climbing fern, Lygodium microphyllum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Old World climbing fern, Lygodium microphyllum is one of the most serious invasive, weeds affecting southern and central Florida. Management of this weed using traditional strategies has proved difficult and expensive, with limited long-term success. In early 2008, a new biological control agent cal...

  17. Novel imidazo[2,1-b]-1,3,4-thiadiazoles as promising antifungal agents against clinical isolate of Cryptococcus neoformans.

    PubMed

    Alwan, Wesam S; Karpoormath, Rajshekhar; Palkar, Mahesh B; Patel, Harun M; Rane, Rajesh A; Shaikh, Mahamadhanif S; Kajee, Afsana; Mlisana, Koleka P

    2015-05-01

    We herein report the synthesis and in vitro antimicrobial evaluation of twenty five novel hybrid derivatives of imidazo [2,1-b]-1,3,4-thiadiazole containing chalcones (5a-o) and Schiff bases (6a-j) against three fungal strains (Candida albicans, Cryptococcus neoformans and Aspergillus niger). Most of the tested compounds displayed substantial anti-fungal activity with MICs ranging between 1.56 and 100 μg/mL. Compounds 5a, 5b and 5n exhibited promising activity against C. neoformans at a MIC 1.56 μg/mL. In addition, compound 5n also demonstrated significant antifungal activity against the clinical isolates of C. neoformans at MIC 3.125 μg/mL. However, moderate activity was observed for these compounds against four bacterial strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) and Mycobacterium tuberculosis (H37Rv). PMID:25847769

  18. 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. PMID:25766747

  19. Novel 1,3-thiazolidin-4-one derivatives as promising anti-Candida agents endowed with anti-oxidant and chelating properties.

    PubMed

    Secci, Daniela; Carradori, Simone; Bizzarri, Bruna; Chimenti, Paola; De Monte, Celeste; Mollica, Adriano; Rivanera, Daniela; Zicari, Alessandra; Mari, Emanuela; Zengin, Gokhan; Aktumsek, Abdurrahman

    2016-07-19

    Pursuing our recent outcomes regarding the antifungal activity of N-substituted 1,3-thiazolidin-4-ones, we synthesized thirty-six new derivatives introducing aliphatic, cycloaliphatic and heteroaromatic moieties at N1-hydrazine connected with C2 position of the thiazolidinone nucleus and functionalizing the lactam nitrogen with differently substituted (NO2, NH2, Cl and F) benzyl groups. These compounds were tested to evaluate their minimum inhibitory concentration (MIC) against several clinical Candida spp. with respect to topical and systemic reference drugs (clotrimazole, fluconazole, ketoconazole, miconazole, tioconazole, amphotericin B). Moreover, anti-oxidant properties were also evaluated by using different protocols including free radical scavenging (DPPH and ABTS), reducing power (CUPRAC and FRAP), metal chelating and phosphomolybdenum assays. Moreover, for the most active derivatives we assessed the toxicity (CC50) against Hep2 human cells in order to characterize them as multi-target agents for fungal infections. PMID:27100030

  20. 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

  1. 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

  2. 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

  3. Molecular perception of interactions between bis(7)tacrine and cystamine-tacrine dimer with cholinesterases as the promising proposed agents for the treatment of Alzheimer's disease.

    PubMed

    Eslami, Mahboobeh; Hashemianzadeh, Seyed Majid; Bagherzadeh, Kowsar; Seyed Sajadi, Seyed Abolfazl

    2016-01-01

    The infamous chronic neurodegenerative disease, Alzheimer's, that starts with short-term memory loss and eventually leads to gradual bodily function decline which has been attributed to the deficiency in brain neurotransmitters, acetylcholine, and butylcholine. As a matter of fact, design of compounds that can inhibit cholinesterases activities (acetylcholinesterase and butylcholinesterase) has been introduced as an efficient method to treat Alzheimer's. Among proposed compounds, bis(7)tacrine (B7T) is recognized as a noteworthy suppressor for Alzheimer's disease. Recently a new analog of B7T, cystamine-tacrine dimer is offered as an agent to detain Alzheimer's complications, even better than the parent compound. In this study, classical molecular dynamic simulations have been employed to take a closer look into the modes of interactions between the mentioned ligands and both cholinesterase enzymes. According to our obtained results, the structural differences in the target enzymes active sites result in different modes of interactions and inhibition potencies of the ligands against both enzymes. The obtained information can help to investigate those favorable fragments in the studied ligands skeletons that have raised the potency of the analog in comparison with the parent compound to design more potent multi target ligands to heal Alzheimer's disease. PMID:26043757

  4. 3-Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective "small molecule" anti-cancer agent taken from labside to bedside: introduction to a special issue.

    PubMed

    Pedersen, Peter L

    2012-02-01

    Although the "Warburg effect", i.e., elevated glucose metabolism to lactic acid (glycolysis) even in the presence of oxygen, has been recognized as the most common biochemical phenotype of cancer for over 80 years, its biochemical and genetic basis remained unknown for over 50 years. Work focused on elucidating the underlying mechanism(s) of the "Warburg effect" commenced in the author's laboratory in 1969. By 1985 among the novel findings made two related most directly to the basis of the "Warburg effect", the first that the mitochondrial content of tumors exhibiting this phenotype is markedly decreased relative to the tissue of origin, and the second that such mitochondria have markedly elevated amounts of the enzyme hexokinase-2 (HK2) bound to their outer membrane. HK2 is the first of a number of enzymes in cancer cells involved in metabolizing the sugar glucose to lactic acid. At its mitochondrial location HK2 binds at/near the protein VDAC (voltage dependent anion channel), escapes inhibition by its product glucose-6-phosphate, and gains access to mitochondrial produced ATP. As shown by others, it also helps immortalize cancer cells, i.e., prevents cell death. Based on these studies, the author's laboratory commenced experiments to elucidate the gene basis for the overexpression of HK2 in cancer. These studies led to both the discovery of a unique HK2 promoter region markedly activated by both hypoxic conditions and moderately activated by several metabolites (e.g., glucose), Also discovered was the promoter's regulation by epigenetic events (i.e., methylation, demethylation). Finally, the author's laboratory turned to the most important objective. Could they selectively and completely destroy cancerous tumors in animals? This led to the discovery in an experiment conceived, designed, and conducted by Young Ko that the small molecule 3-bromopyruvate (3BP), the subject of this mini-review series, is an incredibly powerful and swift acting anticancer agent

  5. A novel class of ethacrynic acid derivatives as promising drug-like potent generation of anticancer agents with established mechanism of action.

    PubMed

    Mignani, Serge; El Brahmi, Nabil; El Kazzouli, Saïd; Eloy, Laure; Courilleau, Delphine; Caron, Joachim; Bousmina, Mosto M; Caminade, Anne-Marie; Cresteil, Thierry; Majoral, Jean-Pierre

    2016-10-21

    The well-known diuretic Ethacrynic acid (EA, Edecrin), showing low anti-proliferative activities, was chemically modified at different positions. The new EA derivatives have been tested in vitro in anti-proliferative assays on both tumor KB (epidermal carcinoma) and leukemia HL60 (promyelocytic) cells suitable targets for anticancer activity. Reduction of the α-β double bond of EA completely abolished anti-cancer activities, whereas introduction of either 2-(4-substituted phenyl)ethanamine (series A) or 4-(4-substituted phenyl)piperazine (series B) moieties generated compounds showing moderate to strong anti-proliferative activities against human cancer cell lines. Several substitutions on the phenyl of these two moieties are tolerated. The mechanism of action of the EA derivatives prepared in this study is more complex than the inhibition of glutathione S-transferase π ascribed as unique effect to EA and might help to overcome tumor resistances. PMID:27448922

  6. A Quantitative Chemical Proteomics Approach to Profile the Specific Cellular Targets of Andrographolide, a Promising Anticancer Agent That Suppresses Tumor Metastasis*

    PubMed Central

    Wang, Jigang; Tan, Xing Fei; Nguyen, Van Sang; Yang, Peng; Zhou, Jing; Gao, Mingming; Li, Zhengjun; Lim, Teck Kwang; He, Yingke; Ong, Chye Sun; Lay, Yifei; Zhang, Jianbin; Zhu, Guili; Lai, Siew-Li; Ghosh, Dipanjana; Mok, Yu Keung; Shen, Han-Ming; Lin, Qingsong

    2014-01-01

    Drug target identification is a critical step toward understanding the mechanism of action of a drug, which can help one improve the drug's current therapeutic regime and expand the drug's therapeutic potential. However, current in vitro affinity-chromatography-based and in vivo activity-based protein profiling approaches generally face difficulties in discriminating specific drug targets from nonspecific ones. Here we describe a novel approach combining isobaric tags for relative and absolute quantitation with clickable activity-based protein profiling to specifically and comprehensively identify the protein targets of andrographolide (Andro), a natural product with known anti-inflammation and anti-cancer effects, in live cancer cells. We identified a spectrum of specific targets of Andro, which furthered our understanding of the mechanism of action of the drug. Our findings, validated through cell migration and invasion assays, showed that Andro has a potential novel application as a tumor metastasis inhibitor. Moreover, we have unveiled the target binding mechanism of Andro with a combination of drug analog synthesis, protein engineering, and mass-spectrometry-based approaches and determined the drug-binding sites of two protein targets, NF-κB and actin. PMID:24445406

  7. 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

  8. 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

  9. 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. PMID:22589483

  10. 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

  11. Cold tapping method shows promise for subsea repair

    SciTech Connect

    Not Available

    1983-07-01

    The Comex/Konsberg Total Marine Norsk project consists of positioning two Kleber plugs into the pipe to isolate the damaged section. In subsea pipe line repair, two main types of damage can be considered: 1. wet buckle; 2. dry buckle. A serious wet buckle means a hole in the line and the line operator will shut down production and flood the line with a corrosion inhibitor in order to minimize pollution and loss of gas. The line is flooded and the repair procedure is conducted without use of ''tapping'' techniques. A standard hyperbaric welding operation can be done by use of wellknown and proven diving methods. A dry buckle or a small leakage means the line is able to keep pressure and move gas. However, a buckle often means an obstruction to pigs. By experience the operator knows that a dry buckle strongly weakens the line and may grow gradually into a wet buckle. Because the operator first wants to keep line output reliability, he prefers to replace the damaged section as soon as the buckle is located.

  12. Non-Addictive Painkiller Shows Promise in Animal Trials

    MedlinePlus

    ... the National Academy of Sciences . SOURCES: Andrew Coop, Ph.D., professor and associate dean, academic affairs, University ... School of Pharmacy, Baltimore; Stephen Waxman, M.D., Ph.D., professor of neurology, Yale University School of ...

  13. Brain Cancer Treatment Shows Promise in Early Trial

    MedlinePlus

    ... Dr. Timothy Cloughesy. He is director of the neuro-oncology program at the University of California, Los ... Michael Vogelbaum, associate director of the brain tumor neuro-oncology center at the Cleveland Clinic. Here's how ...

  14. 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

  15. 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.

  16. Cord-Blood Transplants Show Promise in Leukemia Treatment

    MedlinePlus

    ... a professor of medicine at Case Western Reserve University School of Medicine in Cleveland. Even so, "one ... in pediatric blood and marrow transplantation at Duke University Medical Center in Durham, N.C. Questions remain, ...

  17. 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., ...

  18. Drug Shows Promise Against Rare, Aggressive Skin Cancer

    MedlinePlus

    ... New Orleans, and published online in the New England Journal of Medicine . An oncologist who was not ... annual meeting, New Orleans; April 19, 2016, New England Journal of Medicine online HealthDay Copyright (c) 2016 ...

  19. New bimetallic EMF cell shows promise in direct energy conversion

    NASA Technical Reports Server (NTRS)

    Hesson, J. C.; Shimotake, H.

    1968-01-01

    Concentration cell, based upon a thermally regenerative cell principle, produces electrical energy from any large heat source. This experimental bimetallic EMF cell uses a sodium-bismuth alloy cathode and a pure liquid sodium anode. The cell exhibits reliability, corrosion resistance, and high current density performance.

  20. 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.

  1. Brain Cancer Treatment Shows Promise in Early Trial

    MedlinePlus

    ... sparing healthy cells," said study co-leader Dr. Timothy Cloughesy. He is director of the neuro-oncology ... in months," said study co-lead author Dr. Michael Vogelbaum, associate director of the brain tumor neuro- ...

  2. 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.

  3. 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.

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

    MedlinePlus

    ... that the drug boosted the brain's production of dopamine, a chemical that helps regulate movement. It also ... of certain brain cells -- including ones that produce dopamine, which help regulate movement. For the past 50 ...

  5. 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.

  6. 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

  7. 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…

  8. Economic Path Scheduling for Mobile Agent System on Computer Network

    NASA Astrophysics Data System (ADS)

    Olajubu, E. A.

    Mobile agent technology has a lot of gains to offer network-centric applications. The technology promises to be very suitable for narrow-bandwidth networks by reducing network latency and allowing transparent per-to-per computing. Multi-agent technology had been proposed for many network-centric applications with little or no path scheduling algorithms. This paper describes the need for path scheduling algorithms for agents in multi-agent systems. Traveling salesman problem (TSP) scheme is used to model ordered agents and the unordered agents schedule their path based on random distribution. The two types of agents were modeled and simulated based on bandwidth usage and response time as performance metrics. Our simulation results shows that ordered agents have superior performance against unordered agents. The ordered agents exhibit lower bandwidth usage and higher response time.

  9. "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…

  10. 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.…

  11. 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. PMID:23294232

  12. 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

  13. Promising combination therapies with gemcitabine.

    PubMed

    Robinson, Blaine W; Ostruszka, Leo; Im, Michael M; Shewach, Donna S

    2004-04-01

    Because treatment regimens for breast cancer commonly include gemcitabine, we evaluated two promising combinations in preclinical studies: gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) with either ionizing radiation or docetaxel (Taxotere; Aventis Pharmaceuticals, Inc, Parsippany, NJ). In breast cancer cell lines that expressed either wild-type p53 (MCF-7) or mutant p53 (MCF-7/Adr), sensitivity to the cytotoxic effects of gemcitabine during a 24-hour incubation was similar (IC(50) values 80 and 60 nmol/L in MCF-7 and MCF-7/Adr, respectively). Both cell lines were well radiosensitized by gemcitabine at the corresponding IC(50), with radiation enhancement ratios of 1.6 to 1.7. Although the MCF-7 cells accumulated nearly twice as much gemcitabine triphosphate compared with the MCF-7/Adr cells, a similar reduction in 2'-deoxyadenosine 5'-triphosphate pools was observed. While the number of dying cells, as measured by sub-G1 DNA content or S-phase cells unable to replicate DNA, differed between the wild-type p53 or mutant p53-expressing cell lines, neither parameter correlated with radiosensitization. Docetaxel was a more potent cytotoxic agent than gemcitabine in MCF-7 cells (IC(50) = 1 nmol/L). Strong synergistic cytotoxicity was observed in cells treated with gemcitabine (24 hours) followed by docetaxel (24 hours) or the reverse sequence. However, simultaneous addition of the two drugs was antagonistic. To determine whether synergy with radiation or docetaxel was mediated by increased DNA damage, DNA double-strand breaks (double-strand breaks) were measured by immunostaining for phosphorylated H2AX. Ionizing radiation produced more double-strand breaks than gemcitabine alone, while no significant double-strand breaks formed with docetaxel alone. The addition of docetaxel or ionizing radiation to gemcitabine-treated cells did not increase H2AX foci formation. These results show that the combination of gemcitabine with ionizing radiation or docetaxel

  14. 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.

  15. Radioprotective agents for radiation therapy: future trends.

    PubMed

    Johnke, Roberta M; Sattler, Jennifer A; Allison, Ron R

    2014-12-01

    Only two radioprotective compounds, amifostine and palifermin, currently have the US FDA approval for use in radiation therapy. However, several agents have been reported that show therapeutic promise. Many of these agents are free radical scavengers/antioxidants. Superoxide dismutase and superoxide dismutase mimetics, nitroxides and dietary antioxidants are all being investigated. Recently, alternative strategies of drug development have been evolving, which focus on targeting the series of cellular insult recognition/repair responses initiated following radiation. These agents, which include cytokines/growth factors, angiotensin-converting enzyme inhibitors and apoptotic modulators, show promise of having significant impact on the mitigation of radiation injury. Herein, we review current literature on the development of radioprotectors with emphasis on compounds with proven or potential usefulness in radiation therapy. PMID:25525844

  16. Gaia: Status and Promises

    NASA Astrophysics Data System (ADS)

    Sozzetti, A.

    2015-10-01

    The power of micro-arcsecond (µas) astrometry is about to be unleashed. ESA's Gaia mission, now entering its second year of routine science operations, will soon fulfil its promise for revolutionary science in the countless aspects of Galactic astronomy and astrophysics. I will briefly review the Gaia mission status of operations, and the scenario for intermediate data releases. Iwill then illustrate the potential of µas astrometry for detection and improved characterization of planetary systems in the neighborhood of the Sun.

  17. [Promising technologies in surgery].

    PubMed

    Kotiv, B N; Maĭstrenko, N A

    2013-06-01

    In modern conditions of local wars and armed conflicts, the basic principle of medical care is to reduce injuries stages of medical evacuation, aimed at accelerating the provision of specialized surgical care. In this regard, significantly increases the need for the development and implementation of new high-tech methods that can improve quality of care, both on the battlefield and on the stages of specialized surgical care. A promising direction is the introduction into clinical practice: minimally invasive technologies, the concept of hybrid navigation surgery, operations with the use of laser technology and robotics, advanced and extremely extensive interventions to cancer patients; technology reduces blood loss, use of cell therapy, transplantation techniques, the development of the concept of organ transplantation, lost in combat trauma, the creation of artificial organs and tissues, the creation of personal protective equipment, integrated with a system of combat, etc. PMID:24000635

  18. 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

  19. 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.

  20. Ascomycins: promising agents for the treatment of inflammatory skin diseases.

    PubMed

    Paul, C; Graeber, M; Stuetz, A

    2000-01-01

    Ascomycin derivatives represent a novel class of anti-inflammatory macrolactams currently under development for the treatment of skin diseases. The main biological effect of ascomycins is an inhibition of the synthesis of both Th1 and Th2-type cytokines in target cells. Several compounds are being developed with SDZ ASM 981 being at the most advanced stage. It has high anti-inflammatory activity in animal models of skin inflammation and does not induce skin atrophy. Topical application of SDZ ASM 981 was shown to be effective in atopic dermatitis (AD), allergic contact dermatitis and also in psoriasis under semi-occlusive conditions. In patients with AD, SDZ ASM 981 cream led to consistently low systemic exposure even when applied on large areas of skin. SDZ ASM 981 overcomes the drawbacks of current topical therapies of inflammatory skin diseases as its safety profile is better than that of topical corticosteroids. Studies continue to investigate its efficacy and safety in the treatment of inflammatory skin diseases. PMID:11060661

  1. Cannabinoids: new promising agents in the treatment of neurological diseases.

    PubMed

    Giacoppo, Sabrina; Mandolino, Giuseppe; Galuppo, Maria; Bramanti, Placido; Mazzon, Emanuela

    2014-01-01

    Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug. In fact, the use of compounds containing Cannabis and their introduction in clinical practice is still controversial and strongly limited by unavoidable psychotropic effects. So, overcoming these adverse effects represents the main open question on the utilization of cannabinoids as new drugs for treatment of several pathologies. To date, therapeutic use of cannabinoid extracts is prescribed in patients with glaucoma, in the control of chemotherapy-related vomiting and nausea, for appetite stimulation in patients with anorexia-cachexia syndrome by HIV, and for the treatment of multiple sclerosis symptoms. Recently, researcher efforts are aimed to employ the therapeutic potentials of Cannabis sativa in the modulation of cannabinoid receptor activity within the central nervous system, particularly for the treatment of neurodegenerative diseases, as well as psychiatric and non-psychiatric disorders. This review evaluates the most recent available data on cannabinoids utilization in experimental and clinical studies, and highlights their beneficial effects in the prevention of the main neurological diseases and for the clinical treatment of symptoms with them correlated. PMID:25407719

  2. Antiparasitic agents.

    PubMed

    Rosenblatt, J E

    1999-11-01

    Several important developments have occurred in recent years in the chemotherapy for and prophylaxis of parasitic infections. Although mefloquine is clearly the most effective agent for prevention of chloroquine-resistant falciparum malaria, its use has been compromised by side effects, both real and imagined. Well-designed studies have shown that side effects occur no more frequently with low-dose mefloquine than with chloroquine. Use of mefloquine in pregnant women has not been associated with birth defects, but the incidence of stillbirths may be increased. Malarone is a new agent that combines atovaquone and proguanil, and it may be as effective as mefloquine; however, it is not yet available in the United States. Several newer agents have appeared in response to the development of multidrug resistant Plasmodium falciparum, especially in Southeast Asia. Halofantrine is available for the treatment of mild to moderate malaria due to P. falciparum and for P. vivax infections. Because of severe toxic effects, use of halofantrine should be restricted to only those unusual and rare situations in which other agents cannot be used. Artemisinin (an extract of the Chinese herbal remedy qinghaosu) and two derivatives, artesunate and artemether, are active against multidrug resistant P. falciparum and are widely used in Asia in oral, parenteral, and rectal forms. The antibacterial azithromycin in combination with atovaquone or quinine has now been reported to treat babesiosis effectively in experimental animals and in a few patients. Azithromycin in combination with paromomycin has also shown promise in the treatment of cryptosporidiosis (and toxoplasmosis when combined with pyrimethamine) in patients with the acquired immunodeficiency syndrome (AIDS). Albendazole is currently the only systemic agent available for treatment of microsporidiosis, an infection primarily of patients with AIDS. In addition, albendazole and ivermectin have emerged as effective broad

  3. 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

  4. Theranos phenomenon: promises and fallacies.

    PubMed

    Diamandis, Eleftherios P

    2015-06-01

    Recently, spectacular advances in diagnostic technologies, genomics, etc. offer unprecedented opportunities for widespread testing of asymptomatic individuals, in the hope that this testing will unravel early disease signs which could lead to preventative or more effective therapeutic measures. In particular, one commercial organization, Theranos, promises to revolutionize diagnostics by offering multi-analyte testing at low prices in commercial outlets, thus challenging the current paradigm of targeted and centralized diagnostic testing. In this paper, I analyze the Theranos technology and their promises, and contrast this information with the currently used technologies, to show that most of the company's claims are exaggerated. While it remains to be seen if this technology will revolutionize diagnostics, in this Opinion Paper, I also draw attention of associated issues, such as self-testing and self-interpretation of results, over-testing, over-diagnosis and over-treatment, along with their associated harms. As the public is bombarded daily with new and revolutionary health-related advances, it is time to balance the enthusiasm of the seemingly obvious huge gains, by also explaining the associated possible harms. PMID:26030792

  5. 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.

  6. 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. ...

  7. Diabetic macular edema: New promising therapies

    PubMed Central

    Shamsi, Hanan N Al; Masaud, Jluwi S; Ghazi, Nicola G

    2013-01-01

    The treatment of diabetic macular edema is rapidly evolving. The era of laser therapy is being quickly replaced by an era of pharmacotherapy. Several pharmacotherapies have been recently developed for the treatment of retinal vascular diseases such as diabetic macular edema. Several intravitreal injections or sustained delivery devices have undergone phase 3 testing while others are currently being evaluated. The results of clinical trials have shown the superiority of some of these agents to laser therapy. However, with the availability of several of these newer agents, it may be difficult to individualize treatment options especially those patients respond differently to various therapies. As such, more effort is still needed in order to determine the best treatment regimen for a given patient. In this article, we briefly summarize the major new therapeutic additions for the treatment of diabetic macular edema and allude to some future promising therapies. PMID:24379924

  8. Antifungal agents.

    PubMed

    Ryder, N S

    1999-12-01

    At this year's ICAAC Meeting, new data on approximately 20 different antifungal agents were presented, while no new agents were disclosed. Drugs in late development include the triazoles, voriconazole (Pfizer Ltd) and Sch-56592 (Schering-Plough Corp), and the echinocandins, caspofungin (Merck & Co Inc) and FK-463 (Fujisawa Pharmaceutical Co Ltd). In contrast to previous years, presentations on these and earlier developmental compounds were relatively modest in scope, with few significant new data. Little new information appeared on the most recent novel class of agents, the sordarins (Glaxo Wellcome plc). Early clinical results were presented for FK-463, showing acceptable tolerability and dose-dependent efficacy in AIDS-associated esophageal candidiasis. A new liposomal formulation of nystatin (Nyotran; Aronex Pharmaceuticals Inc) was shown to be equivalent to conventional amphotericin B in empiric therapy of presumed fungal infection in neutropenic patients, but with reduced toxicity. Intravenous itraconazole (Janssen Pharmaceutica NV) was an effective prophylactic therapy in invasive pulmonary aspergillosis, while oral itraconazole was discussed as a treatment for fungal infection in heart and liver transplant patients. The allylamine compound, terbinafine (Novartis AG), showed good clinical efficacy against fungal mycetoma, a serious tropical infection. A major highlight was the first presentation of inhibitors of fungal efflux pumps as a strategy for overcoming resistance. MC-510027 (milbemycin alpha-9; Microcide Pharmaceuticals Inc) and its derivatives, potentiated the antifungal activity of triazoles and terbinafine in a number of Candida spp. Another pump inhibitor, MC-005172 (Microcide Pharmaceuticals Inc) showed in vivo potentiation of fluconazole in a mouse kidney infection model. Microcide Pharmaceuticals Inc also presented inhibitors of bacterial efflux pumps. PMID:16113946

  9. The Ambivalence of Promising Technology.

    PubMed

    Shelley-Egan, Clare

    2010-08-01

    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

  10. 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.

  11. Biologic agents in juvenile spondyloarthropathies.

    PubMed

    Katsicas, María Martha; Russo, Ricardo

    2016-01-01

    The juvenile spondyloarthropathies (JSpA) are a group of related rheumatic diseases characterized by involvement of peripheral large joints, axial joints, and entheses (enthesitis) that begin in the early years of life (prior to 16(th) birthday).The nomenclature and concept of spondyloarthropathies has changed during the last few decades. Although there is not any specific classification of JSpA, diseases under the spondyloarthropathy nomenclature umbrella in the younger patients include: the seronegative enthesitis and arthropathy (SEA) syndrome, juvenile ankylosing spondylitis, reactive arthritis, and inflammatory bowel disease-associated arthritis. Moreover, the ILAR criteria for Juvenile Idiopathic Arthritis includes two categories closely related to spondyloarthritis: Enthesitis-related arthritis and psoriatic arthritis.We review the pathophysiology and the use of biological agents in JSpA. JSpA are idiopathic inflammatory diseases driven by an altered balance in the proinflammatory cytokines. There is ample evidence on the role of tumor necrosis factor (TNF) and interleukin-17 in the physiopathology of these entities. Several non-biologic and biologic agents have been used with conflicting results in the treatment of these complex diseases. The efficacy and safety of anti-TNF agents, such as etanercept, infliximab and adalimumab, have been analysed in controlled and uncontrolled trials, usually showing satisfactory outcomes. Other biologic agents, such as abatacept, tocilizumab and rituximab, have been insufficiently studied and their role in the therapy of SpA is uncertain. Interleukin-17-blocking agents are promising alternatives for the treatment of JSpA patients in the near future. Recommendations for the treatment of patients with JSpA have recently been proposed and are discussed in the present review. PMID:26968522

  12. 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…

  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. Gadofullerene MRI contrast agents.

    PubMed

    Bolskar, Robert D

    2008-04-01

    A promising new class of MRI contrast-enhancing agents with high relaxivities is based on gadolinium-containing metallofullerenes, which are also termed gadofullerenes. Detailed study of the water-proton relaxivity properties and intermolecular nanoclustering behavior of gadofullerene derivatives has revealed valuable information about their relaxivity mechanisms and given a deeper understanding of this new class of paramagnetic contrast agent. Here, the latest findings on water-solubilized gadofullerene materials and how these findings relate to their future applications in MRI are reviewed and discussed. PMID:18373426

  15. 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

  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. 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

  18. Is Technology Fulfilling Its Promise?

    ERIC Educational Resources Information Center

    Weinstein, Margery

    2011-01-01

    Technology has promised trainers so much--from the ability to train distant learners to new ways of keeping young employees engaged. But has it delivered? In this article, several trainers consider whether their investment in training technology has been worth it.

  19. The Promise of Transformative Partnerships

    ERIC Educational Resources Information Center

    Yendol-Hoppey, Diane

    2010-01-01

    The promise, potential, and problems associated with school-university partnerships interested in better preparing teachers for the challenges they face teaching in today's schools rest in educators' ability to actualize transformative practices within partnership contexts. To date, most partnerships have focused on less complex forms of…

  20. The Educational Promise of Logo.

    ERIC Educational Resources Information Center

    Maddux, Cleborne D.

    1984-01-01

    Discussion of Logo use to teach children computer programing covers the educational theory behind Logo, how it differs from other programing languages, its educational promise, its graphics capabilities, Logo research, and different versions available. It is argued that educational computing will succeed only if it provides new ways of teaching.…

  1. 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.

  2. 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…

  3. Educating Homeless Students: Promising Practices.

    ERIC Educational Resources Information Center

    Stronge, James H., Ed.; Reed-Victor, Evelyn, Ed.

    This book is for educators who serve homeless students or students temporarily sharing houses with other families. It describes many promising strategies for working with these students. The chapters are: (1) "Educating Homeless Children and Youth: An Introduction" (James H. Stronge); (2) "Meeting the Developmental and Educational Needs of…

  4. 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

  5. Enediyne compounds - new promises in anticancer therapy.

    PubMed

    Gredicak, Matija; Jerić, Ivanka

    2007-06-01

    Scientists of all kinds have long been intrigued by the nature, action and potential of natural toxins that possess exceptional antibacterial and anticancer activities. These compounds, named enediynes, are among the most effective chemotherapeutic agents known. Often compared with intelligent weapons, due to the unique structure and sophisticated mechanism by which they destroy double-helical DNA, enediyne antibiotics are nowadays the most promising leaders in the anticancer therapy. Apart from their diversity, enediyne compounds share some structural and functional similarities. One fragment of a structure is responsible for the recognition and transport, another part acts as molecular trigger while the third, reactive enediyne unit, undergoes Bergman cycloaromatization and causes DNA breakage. Members of the enediyne family are already in clinical use to treat various cancers, but more general use is limited by their complex structure, which makes them formidable targets for synthetic chemists. There are three main approaches in the design of new enediyne-related compounds: improvement of enediyne >warheads<, increasing the selectivity and control of chemical or photo-induced activation. This paper gives an overview of naturally occurring enediynes, their mode of action and efforts undertaken to design artificial enediyne-related DNA cleaving agents. PMID:17507311

  6. 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.

  7. The promise of quantum simulation

    DOE PAGESBeta

    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. The Promise of Quantum Simulation.

    PubMed

    Muller, Richard P; Blume-Kohout, Robin

    2015-08-25

    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. PMID:26197037

  10. X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents.

    PubMed

    Rand, Danielle; Uchida, Masaki; Douglas, Trevor; Rose-Petruck, Christoph

    2014-09-22

    Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorption-based x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based "nanobubble" contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size. PMID:25321797

  11. X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents

    PubMed Central

    Rand, Danielle; Uchida, Masaki; Douglas, Trevor; Rose-Petruck, Christoph

    2014-01-01

    Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorption-based x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based “nanobubble” contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size. PMID:25321797

  12. New agents for prostate cancer.

    PubMed

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

    2014-09-01

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

  13. 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.

  14. Graphene-based contrast agents for photoacoustic and thermoacoustic tomography☆

    PubMed Central

    Lalwani, Gaurav; Cai, Xin; Nie, Liming; Wang, Lihong V.; Sitharaman, Balaji

    2013-01-01

    In this work, graphene nanoribbons and nanoplatelets were investigated as contrast agents for photoacoustic and thermoacoustic tomography (PAT and TAT). We show that oxidized single- and multi-walled graphene oxide nanoribbons (O-SWGNRs, O-MWGNRs) exhibit approximately 5–10 fold signal enhancement for PAT in comparison to blood at the wavelength of 755 nm, and approximately 10–28% signal enhancement for TAT in comparison to deionized (DI) water at 3 GHz. Oxidized graphite microparticles (O-GMPs) and exfoliated graphene oxide nanoplatelets (O-GNPs) show no significant signal enhancement for PAT, and approximately 12–29% signal enhancement for TAT. These results indicate that O-GNRs show promise as multi-modal PAT and TAT contrast agents, and that O-GNPs are suitable contrast agents for TAT. PMID:24490141

  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. 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

  17. 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...

  18. 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...

  19. NIH-Supported Study Shows Promise for Blood Test for Alzheimer's Disease

    MedlinePlus

    ... years before symptoms develop. The test measured the levels of several tau and amyloid proteins—the hallmarks of Alzheimer’s disease—in exosomes, microscopic organelles shed by brain cells. The study by Dimitrios Kapogiannis, Ph.D., and Edward Goetzl, M.D., both of ...

  20. Noise-injected neural networks show promise for use on small-sample expression data

    PubMed Central

    Hua, Jianping; Lowey, James; Xiong, Zixiang; Dougherty, Edward R

    2006-01-01

    Background Overfitting the data is a salient issue for classifier design in small-sample settings. This is why selecting a classifier from a constrained family of classifiers, ones that do not possess the potential to too finely partition the feature space, is typically preferable. But overfitting is not merely a consequence of the classifier family; it is highly dependent on the classification rule used to design a classifier from the sample data. Thus, it is possible to consider families that are rather complex but for which there are classification rules that perform well for small samples. Such classification rules can be advantageous because they facilitate satisfactory classification when the class-conditional distributions are not easily separated and the sample is not large. Here we consider neural networks, from the perspectives of classical design based solely on the sample data and from noise-injection-based design. Results This paper provides an extensive simulation-based comparative study of noise-injected neural-network design. It considers a number of different feature-label models across various small sample sizes using varying amounts of noise injection. Besides comparing noise-injected neural-network design to classical neural-network design, the paper compares it to a number of other classification rules. Our particular interest is with the use of microarray data for expression-based classification for diagnosis and prognosis. To that end, we consider noise-injected neural-network design as it relates to a study of survivability of breast cancer patients. Conclusion The conclusion is that in many instances noise-injected neural network design is superior to the other tested methods, and in almost all cases it does not perform substantially worse than the best of the other methods. Since the amount of noise injected is consequential, the effect of differing amounts of injected noise must be considered. PMID:16737545

  1. 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

  2. DRAINAGE PIPE DETECTOR: GROUND PENETRATING RADAR SHOWS PROMISE IN LOCATING BURIED SYSTEMS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the more frustrating problems confronting farmers and land improvement contractors in the Midwestern United States involves locating buried agricultural drainage pipes. Conventional geophysical methods, particularly ground penetrating radar (GPR), presently being used for environmental and co...

  3. 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.

  4. Promising treatments in development for food allergies.

    PubMed

    Rancé, Fabienne

    2004-11-01

    Up to 6% of young children and 2% of adults suffer from food allergy. Among them many have IgE-mediated food allergy, a condition with potentially fatal allergic reactions. The only proven treatment is avoidance of the offending food, which can be identified using standardised allergic tests. However, several studies have addressed possible definite treatment options for food allergy. Immunotherapy, administered orally or by systemic injections, shows promising preliminary results, but these therapeutics are based on studies with insufficient scientific support, or are associated with a high risk of severe side effects. At present, no studies can support pharmacotherapy. However, promising results were recently published with anti-IgE antibodies in a human trial, and various approaches in a mouse model of food allergy (chinese herbal medicine, specific modulation of the T-cell response). Rapidly evolving findings might provide hope for a cure for food allergy in the near future. PMID:15571483

  5. [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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. Resveratrol as promising natural radioprotector. A review.

    PubMed

    Dobrzyńska, Małgorzata M

    2013-01-01

    Public feelings concerning radiation are still controversy. The main sources of trouble seems to be the failure nuclear power plant and danger of terroristic attack, which may cause temporally enhanced level of radiation leading to harmful health effects. Since radiation induced cellular damage is attributed primarily to harmful effect of free radicals, molecules with direct free radical scavenging properties are particularly promising as radiation modifiers/protectors, i.e. agents which present prior to or shortly after radiation exposure alter to response of tissues to radiation. Unfortunately, some of known radioprotectors are toxic at doses required for radioprotection. Resveratrol (RSV), an natural polyphenol is produced in several plants in response to injury, stress, bacteria or fungi infection, UV-irradiation and exposure to ozone. It is present in human diet i.e. in fruits and in wine. RSV is known for its antioxidant, anti-inflammatory, analgesic, antiviral, cardioprotective, neuroprotective and antiageing action and it has been shown to have chemopreventive effects with respect to several human disease such as cardiovascular disease, osteoporosis and gastric ulcers. Depending on the dose, RSV may act as antioxidant or as pro-oxidant. RSV improves sperm count and motility in rodents and prevent DNA damage caused by cryptopreservation of human sperm. Moreover, RSV acting with other agents, inhibits the toxic action of them. There are evidences that RSV is able to modulate the behavior of cells in response to radiation induced damage. Minimalization of radiation induced damage to somatic and germ cells by RSV might be useful in cancer therapy to prevent the damage to normal cells as well as in case of radiological accidents. PMID:24693709

  12. 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…

  13. Promising candidates for allergy prevention.

    PubMed

    Gern, James E

    2015-07-01

    Recent advances in understanding environmental risk factors for allergic diseases in children have 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 might 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 effect for the prevention of childhood allergic diseases and explores possible strategies for enhancing exposure to beneficial microbes. PMID:26145984

  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. 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

  16. MFTF-progress and promise

    SciTech Connect

    Thomassen, K.I.

    1980-10-03

    The Mirror Fusion Test Facility (MFTF) has been in construction at Lawrence Livermore National Laboratory (LLNL) for 3 years, and most of the major subsystems are nearing completion. Recently, the scope of this project was expanded to meet new objectives, principally to reach plasma conditions corresponding to energy break-even. To fulfill this promise, the single-cell minimum-B mirror configuration will be replaced with a tandem mirror configuration (MFTF-B). The facility must accordingly be expanded to accomodate the new geometry. This paper briefly discusses the status of the major MFTF subsystems and describes how most of the technological objectives of MFTF will be demonstrated before we install the additional systems necessary to make the tandem. It also summarizes the major features of the expanded facility.

  17. 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

  18. 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

  19. The neural circuitry of a broken promise.

    PubMed

    Baumgartner, Thomas; Fischbacher, Urs; Feierabend, Anja; Lutz, Kai; Fehr, Ernst

    2009-12-10

    Promises are one of the oldest human-specific psychological mechanisms fostering cooperation and trust. Here, we study the neural underpinnings of promise keeping and promise breaking. Subjects first make a promise decision (promise stage), then they anticipate whether the promise affects the interaction partner's decision (anticipation stage) and are subsequently free to keep or break the promise (decision stage). Findings revealed that the breaking of the promise is associated with increased activation in the DLPFC, ACC, and amygdala, suggesting that the dishonest act involves an emotional conflict due to the suppression of the honest response. Moreover, the breach of the promise can be predicted by a perfidious brain activity pattern (anterior insula, ACC, inferior frontal gyrus) during the promise and anticipation stage, indicating that brain measurements may reveal malevolent intentions before dishonest or deceitful acts are actually committed. PMID:20005830

  20. 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

  1. Cannabidiol: a promising drug for neurodegenerative disorders?

    PubMed

    Iuvone, Teresa; Esposito, Giuseppe; De Filippis, Daniele; Scuderi, Caterina; Steardo, Luca

    2009-01-01

    Neurodegenerative diseases represent, nowadays, one of the main causes of death in the industrialized country. They are characterized by a loss of neurons in particular regions of the nervous system. It is believed that this nerve cell loss underlies the subsequent decline in cognitive and motor function that patients experience in these diseases. A range of mutant genes and environmental toxins have been implicated in the cause of neurodegenerative disorders but the mechanism remains largely unknown. At present, inflammation, a common denominator among the diverse list of neurodegenerative diseases, has been implicated as a critical mechanism that is responsible for the progressive nature of neurodegeneration. Since, at present, there are few therapies for the wide range of neurodegenerative diseases, scientists are still in search of new therapeutic approaches to the problem. An early contribution of neuroprotective and antiinflammatory strategies for these disorders seems particularly desirable because isolated treatments cannot be effective. In this contest, marijuana derivatives have attracted special interest, although these compounds have always raised several practical and ethical problems for their potential abuse. Nevertheless, among Cannabis compounds, cannabidiol (CBD), which lacks any unwanted psychotropic effect, may represent a very promising agent with the highest prospect for therapeutic use. PMID:19228180

  2. The Wordpath Show.

    ERIC Educational Resources Information Center

    Anderton, Alice

    The Intertribal Wordpath Society is a nonprofit educational corporation formed to promote the teaching, status, awareness, and use of Oklahoma Indian languages. The Society produces "Wordpath," a weekly 30-minute public access television show about Oklahoma Indian languages and the people who are teaching and preserving them. The show aims to…

  3. 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

  4. 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.

  5. Promising ethanologens for xylose fermentation

    SciTech Connect

    Zhang, M.; Franden, M.A.; Newman, M.

    1995-12-31

    An economical biomass-to-ethanol process depends on the efficient conversion of both its cellulose and hemicellulose components. On a dry weight basis, the typical feedstock contains approx 25-50% (w/w) glucose, 10-30% (w/w) xylose, 15-30% (w/w) lignin, and 1-5% (w/w) of other minor pentose and hexose sugars. Although many microorganisms can ferment the glucose component in cellulose to ethanol, conversion of pentose sugars in the hemicellulose fraction, particularly xylose, has been hindered by the lack of a suitable biocatalyst. Despite the development of recombinant strains with improved fermentation performance, increased ethanol yields and concentrations and shorter fermentation times are key targets that have yet to be achieved from lignocellulosic hydrolyzates. Our objective is to develop biocatalysts for the rapid and efficient conversion of xylose by engineering key metabolic pathways in selected organisms. To identify promising biocatalysts for these efforts, we have surveyed several industrial microorganisms according to several primary traits considered to be essential, as well as a number of secondary traits considered to be desirable, in a commercial biomass-to-ethanol process.

  6. 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.

  7. 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)

  8. 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…

  9. 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…

  10. 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)

  11. 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)

  12. Talk Show Science.

    ERIC Educational Resources Information Center

    Moore, Mitzi Ruth

    1992-01-01

    Proposes having students perform skits in which they play the roles of the science concepts they are trying to understand. Provides the dialog for a skit in which hot and cold gas molecules are interviewed on a talk show to study how these properties affect wind, rain, and other weather phenomena. (MDH)

  13. 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…

  14. 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…

  15. Scanning surface-enhanced Raman spectroscopy (SERS) of chemical agent simulants on templated Au-Ag nanowire substrates

    NASA Astrophysics Data System (ADS)

    Hoffmann, J. A.; Miragliotta, J. A.; Wang, J.; Tyagi, P.; Maddanimath, T.; Gracias, D. H.; Papadakis, S. J.

    2009-05-01

    We report the results of scanning micro-Raman spectroscopy obtained on Au-Ag nanowires for a variety of chemical warfare agent simulants. Rough silver segments embedded in gold nanowires showed enhancement of 105 - 107 and allowed unique identification of 3 of 4 chemical agent simulants tested. These results suggest a promising method for detection of compounds significant for security applications, leading to sensors that are compact and selective.

  16. AMLCD cockpit: promise and payoffs

    NASA Astrophysics Data System (ADS)

    Snow, Michael P.; Jackson, Timothy W.; Meyer, Frederick M.; Reising, John M.; Hopper, Darrel G.

    1999-08-01

    optical characterization of the AMLCDs used in this simulator and the cockpit design are described. Display formats under consideration for test in this cockpit are described together with some of the basic human factors engineering issues involved. Studies conducted in this cockpit will be part of an ongoing joint effort of the hardware-focused aerospace displays team and the pilot-focused human factors team in the Air Force Research Laboratory's Crew System Interface Division. The objective of these studies is to ascertain the payoffs of the large AMLCD promise in combat cockpits.

  17. 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;…

  18. 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

  19. Promises and Self-Focused Attention.

    ERIC Educational Resources Information Center

    Callahan, Sidney

    Making a promise involves a self-conscious, self-commitment to undertake an obligation in the future and involves a personal sense of control. To study promises and self-focused attention, 72 women completed measures of self-focused attention and locus of control, a questionnaire, and were asked to promise to return postcards. As predicted,…

  20. 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

  1. 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.

  2. 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

  3. 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

  4. Learning models of intelligent agents

    SciTech Connect

    Carmel, D.; Markovitch, S.

    1996-12-31

    Agents that operate in a multi-agent system need an efficient strategy to handle their encounters with other agents involved. Searching for an optimal interactive strategy is a hard problem because it depends mostly on the behavior of the others. In this work, interaction among agents is represented as a repeated two-player game, where the agents` objective is to look for a strategy that maximizes their expected sum of rewards in the game. We assume that agents` strategies can be modeled as finite automata. A model-based approach is presented as a possible method for learning an effective interactive strategy. First, we describe how an agent should find an optimal strategy against a given model. Second, we present an unsupervised algorithm that infers a model of the opponent`s automaton from its input/output behavior. A set of experiments that show the potential merit of the algorithm is reported as well.

  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. Radioprotective Agents: Strategies and Translational Advances.

    PubMed

    Kamran, Mohammad Zahid; Ranjan, Atul; Kaur, Navrinder; Sur, Souvik; Tandon, Vibha

    2016-04-01

    Radioprotectors are agents required to protect biological system exposed to radiation, either naturally or through radiation leakage, and they protect normal cells from radiation injury in cancer patients undergoing radiotherapy. It is imperative to study radioprotectors and their mechanism of action comprehensively, looking at their potential therapeutic applications. This review intimately chronicles the rich intellectual, pharmacological story of natural and synthetic radioprotectors. A continuous effort is going on by researchers to develop clinically promising radioprotective agents. In this article, for the first time we have discussed the impact of radioprotectors on different signaling pathways in cells, which will create a basis for scientific community working in this area to develop novel molecules with better therapeutic efficacy. The bright future of exceptionally noncytotoxic derivatives of bisbenzimidazoles is also described as radiomodulators. Amifostine, an effective radioprotectant, has been approved by the FDA for limited clinical use. However, due to its adverse side effects, it is not routinely used clinically. Recently, CBLB502 and several analog of a peptide are under clinical trial and showed high success against radiotherapy in cancer. This article reviews the different types of radioprotective agents with emphasis on the strategies for the development of novel radioprotectors for drug development. In addition, direction for future strategies relevant to the development of radioprotectors is also addressed. PMID:26807693

  7. 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.

  8. 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.

  9. Other potentially useful new injectable anesthetic agents.

    PubMed

    Ilkiw, J E

    1992-03-01

    Ultrashort barbiturates are not ideal injectable anesthetic agents, and new agents continue to be released as investigators pursue the goal of finding a more ideal agent. Of the new injectable agents discussed, propofol seems to be the most promising drug. Propofol should find a place in veterinary practice as an outpatient anesthetic agent because it has a rapid, smooth, and complete recovery even after repeated or continuous administration. Midazolam does not induce anesthesia in healthy, small animals and, as such, can only be used in combination with other injectable agents, such as ketamine or the thiobarbiturates. In our practice, Telazol has found a place in the anesthetic management of feral cats and aggressive dogs, where it is used for heavy sedation or to induce anesthesia. The role of flumazenil, as a reversal agent, in veterinary practice remains to be determined; however, the role in small domestic animals is unlikely to be significant. PMID:1585555

  10. 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.

  11. Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug.

    PubMed

    Cardaci, Simone; Desideri, Enrico; Ciriolo, Maria Rosa

    2012-02-01

    The Warburg effect refers to the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions. Although the molecular mechanisms underlying tumor reliance on glycolysis remains not completely clear, its inhibition opens feasible therapeutic windows for cancer treatment. Indeed, several small molecules have emerged by combinatorial studies exhibiting promising anticancer activity both in vitro and in vivo, as a single agent or in combination with other therapeutic modalities. Therefore, besides reviewing the alterations of glycolysis that occur with malignant transformation, this manuscript aims at recapitulating the most effective pharmacological therapeutics of its targeting. In particular, we describe the principal mechanisms of action and the main targets of 3-bromopyruvate, an alkylating agent with impressive antitumor effects in several models of animal tumors. Moreover, we discuss the chemo-potentiating strategies that would make unparalleled the putative therapeutic efficacy of its use in clinical settings. PMID:22328057

  12. 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.

  13. 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.

  14. 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...

  15. A Novel Isoquinoline Derivative Anticancer Agent and Its Targeted Delivery to Tumor Cells Using Transferrin-Conjugated Liposomes

    PubMed Central

    Yang, Xuewei; Yang, Shuang; Chai, Hongyu; Yang, Zhaogang; Lee, Robert J.; Liao, Weiwei; Teng, Lesheng

    2015-01-01

    We have screened 11 isoquinoline derivatives and α-methylene-γ-butyrolactones using the 3-(4,5-dimethylthi-azol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay in HeLa and HEK-293T cells. Compound 2 was identified as potential anticancer agent. To further improve its therapeutic potential, this agent was incorporated into transferrin (Tf)-conjugated liposomes (LPs) for targeted delivery to tumor cells. We have demonstrated Tf-LP-Compound 2 have superior antitumor activity compared to non-targeted controls and the free drug. These data show Tf-LP-Compound 2 to be a promising agent that warrants further evaluation. PMID:26309138

  16. 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

  17. 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 ...

  18. 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…

  19. 32 CFR 806b.9 - Confidentiality promises.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Confidentiality promises. 806b.9 Section 806b.9 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION PRIVACY ACT PROGRAM Obtaining Law Enforcement Records and Confidentiality Promises § 806b.9 Confidentiality...

  20. 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.

  1. Agent Building Software

    NASA Technical Reports Server (NTRS)

    2000-01-01

    AgentBuilder is a software component developed under an SBIR contract between Reticular Systems, Inc., and Goddard Space Flight Center. AgentBuilder allows software developers without experience in intelligent agent technologies to easily build software applications using intelligent agents. Agents are components of software that will perform tasks automatically, with no intervention or command from a user. AgentBuilder reduces the time and cost of developing agent systems and provides a simple mechanism for implementing high-performance agent systems.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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 ...

  9. AmeriCorps Promise Fellows Handbook: Delivering on America's Promise to Youth.

    ERIC Educational Resources Information Center

    Corporation for National Service, Washington, DC.

    This handbook provides AmeriCorps Promise Fellows with important information about their participation in this special initiative of AmeriCorps and America's Promise--The Alliance for Youth. Section 1 is an overview of AmeriCorps, including its mission, the mission of America's Promise--The Alliance for Youth, and the role of AmeriCorps Promise…

  10. 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.

  11. 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.

  12. 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.

  13. Investigational antimicrobial agents of 2013.

    PubMed

    Pucci, Michael J; Bush, Karen

    2013-10-01

    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

  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. 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.

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

    PubMed

    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

  17. 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

  18. 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

  19. 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

  20. Dopamine and the cognitive downside of a promised bonus

    PubMed Central

    Aarts, Esther; Wallace, Deanna L.; Dang, Linh C.; Jagust, William; Cools, Roshan; D'Esposito, Mark

    2014-01-01

    It is often assumed that the promise of a monetary bonus improves cognitive control. We show that in fact appetitive motivation can also impair cognitive control, depending on baseline levels of dopamine synthesis capacity in the striatum. These data demonstrate not only that appetitive motivation can have paradoxical detrimental effects for cognitive control, but also provide a mechanistic account of these effects. PMID:24525265

  1. 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…

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Endogenizing geopolitical boundaries with agent-based modeling.

    PubMed

    Cederman, Lars-Erik

    2002-05-14

    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

  7. 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

  8. Realising the Promise of Cancer Predisposition Genes

    PubMed Central

    Rahman, Nazneen

    2016-01-01

    Genes in which germline mutations confer high or moderate increased risks of cancer are called cancer predisposition genes (CPG). Over 100 CPGs have been identified providing important scientific insights in many areas, particularly mechanisms of cancer causation. Moreover, clinical utilisation of CPGs has had substantial impact in diagnosis, optimised management and prevention of cancer. The recent transformative advances in DNA sequencing bring the promise of many more CPG discoveries and greater, broader clinical applications. However, there is also considerable potential for incorrect inferences and inappropriate clinical applications. Realising the promise of cancer predisposition genes for science and medicine will thus require careful navigation. PMID:24429628

  9. Stem cell research and economic promises.

    PubMed

    Caulfield, Timothy

    2010-01-01

    In the context of stem cell research, the promise of economic growth has become a common policy argument for adoption of permissive policies and increased government funding. However, declarations of economic and commercial benefit, which can be found in policy reports, the scientific literature, public funding policies, and the popular press, have arguably created a great deal of expectation. Can stem cell research deliver on the economic promise? And what are the implications of this economic ethos for the researchers who must work under its shadow? PMID:20579253

  10. 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

  11. 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

  12. Injectable agents affecting subcutaneous fats.

    PubMed

    Chen, David Lk; Cohen, Joel L; Green, Jeremy B

    2015-09-01

    Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. PMID:26566569

  13. 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.

  14. Profiles of Selected Promising Professional Development Initiatives.

    ERIC Educational Resources Information Center

    Cohen, Carol; Gerber, Peter; Handley, Claire; Kronley, Robert; Parry, Megan

    In 2000, the Finance Project received a planning grant to launch a new initiative on financing professional development in education. This report represents efforts to identify and develop a database on promising new approaches to professional development in education, profiling 16 initiatives recommended by knowledge experts and representing a…

  15. Alcohol Research: Promise for the Decade.

    ERIC Educational Resources Information Center

    Gordis, Enoch

    Over the past 20 years, alcohol researchers have made intensive efforts to understand alcohol use and its outcomes. To date, researchers have made much progress toward understanding the causes and consequences of alcoholism and its related problems. This publication attempts to convey the great spirit and promise of alcohol research. Established…

  16. 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…

  17. 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…

  18. Objectification Theory: Areas of Promise and Refinement

    ERIC Educational Resources Information Center

    Moradi, Bonnie

    2011-01-01

    This article elaborates on three themes related to Szymanski, Moffitt, and Carr's major contribution aims. First, the article describes the promise of objectification theory as a grounding framework in research and practice, outlining how this theory integrates key aspects of several other important theoretical models. Second, this article…

  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. 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…

  1. 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…

  2. 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…

  3. 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...

  4. 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…

  5. 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…

  6. Distance Learning: Promises, Problems, and Possibilities.

    ERIC Educational Resources Information Center

    Valentine, Doug

    2002-01-01

    Examines some of the current research and thought on the promises, problems, and the future possibilities in modern distance learning, particularly types that are delivered via electronic means. Topics include history of distance learning; quality of instruction; cost effectiveness; misuse of technology; equipment problems; instructor attitudes…

  7. 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

  8. 2. DETAIL OF EAST FRONT, SHOWING DISPATCH OFFICE / DISTRICT ...

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

    2. DETAIL OF EAST FRONT, SHOWING DISPATCH OFFICE / DISTRICT TRAFFIC AGENT'S PROJECTION. VIEW TO SOUTHWEST. - Commercial & Industrial Buildings, Illinois Central Railroad Passenger Depot, Iowa & Jones Streets, Dubuque, Dubuque County, IA

  9. Sulforaphane as a promising molecule for fighting cancer.

    PubMed

    Lenzi, Monia; Fimognari, Carmela; Hrelia, Patrizia

    2014-01-01

    Cancer is a complex disease characterized by multiple genetic and molecular alterations involving transformation, deregulation of apoptosis, proliferation, invasion, angiogenesis, and metastasis. To grow, invade, and metastasize, tumors need host components and primary dysfunction in the tumor microenvironment, in addition to cell dysfunction, can be crucial for carcinogenesis. A great variety of phytochemicals have been shown to be potentially capable of inhibiting and modulating several relevant targets simultaneously and is therefore non-specific. Because of the enormous biological diversity of cancer, this pleiotropism might constitute an advantage. Phytochemicals, in particular diet-derived compounds, have therefore been proposed and applied in clinical trials as cancer chemopreventive/chemotherapeutic agents. Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables. SFN has proved to be an effective chemoprotective agent in cell culture, in carcinogen-induced and genetic animal cancer models, as well as in xenograft models of cancer. It promoted potent cytostatic and cytotoxic effects orchestrated by the modulation of different molecular targets. Cell vulnerability to SFN-mediated apoptosis was subject to regulation by cell-cycle-dependent mechanisms but was independent of a mutated p53 status. Moreover, combination of SFN with cytotoxic therapy potentiated the cytotoxic effect mediated by chemotherapy in vitro, thus suggesting its potential therapeutic benefit in clinical settings. Overall, SFN appears to be an effective and safe chemopreventive molecule and a promising tool to fight cancer. PMID:24114482

  10. A Multi-agent Approach to Distribution System Restoration

    NASA Astrophysics Data System (ADS)

    Nagata, Takeshi; Tao, Yasuhiro; Sasaki, Hiroshi; Fujita, Hideki

    This paper proposes a multi-agent approach to decentralized power system restoration for a distribution system network. The proposed method consists of several Feeder Agents (FAGs) and Load Agents (LAGs). LAG corresponds to the customer load, while a FAG is developed to act as a manager for the decision process. From the simulation results, it can be seen the proposed multi-agent system could reach the right solution by making use of only local information. This means that the proposed multi-agent restoration system is a promising approach to more large-scale distribution networks.

  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. Pyrazolo[3,4-h]quinolines promising photosensitizing agents in the treatment of cancer.

    PubMed

    Spanò, Virginia; Parrino, Barbara; Carbone, Anna; Montalbano, Alessandra; Salvador, Alessia; Brun, Paola; Vedaldi, Daniela; Diana, Patrizia; Cirrincione, Girolamo; Barraja, Paola

    2015-09-18

    A new series of pyrazolo[3,4-h]quinolines, heteroanalogues of angelicin was conveniently prepared with a broad substitution pattern. A large number of derivatives was obtained and the cellular photocytotoxicity was evaluated in vitro against 5 different human tumor cell lines with GI50 values reaching the nanomolar level (14.52-0.04 μM). Selected compounds were able to photoinduce a massive cell death with the involvement of mitochondria. Their photodamage cellular targets were proteins and lipids and they did not cause any kind of DNA photodamage. This latter event is of considerable importance in the modulation of long term side effects, generally associated with the use of classical furocoumarins. PMID:26295175

  14. Aurones: A Promising Heterocyclic Scaffold for the Development of Potent Antileishmanial Agents

    PubMed Central

    Roussaki, Marina; Costa Lima, Sofia; Kypreou, Anna-Maria; Kefalas, Panagiotis; Cordeiro da Silva, Anabela; Detsi, Anastasia

    2012-01-01

    A series of (Z)-2-benzylidenebenzofuran-3-(2H)-ones (aurones) bearing a variety of substituents on rings A and B were synthesized and evaluated for their antiparasitic activity against the intracellular amastigote form of Leishmania infantum and their cytotoxicity against human THP1-differentiated macrophages. In general, aurones bearing no substituents on ring A (compounds 4a–4f) exhibit higher toxicity than aurones with 4,6-dimethoxy substitution (compounds 4g–4l). Among the latter, two aurones possessing a 2′-methoxy or a 2′-methyl group (compounds 4i and 4j) exhibit potent antileishmanial activity (IC50 = 1.3 ± 0.1 μM and IC50 = 1.6 ± 0.2 μM, resp.), comparable to the activity of the reference drug Amphotericin B, whereas they present significantly lower cytotoxicity than Amphotericin B as deduced by the higher selectivity index. PMID:25374683

  15. Natural Products as Promising Antitumoral Agents in Breast Cancer: Mechanisms of Action and Molecular Targets.

    PubMed

    Bonofiglio, Daniela; Giordano, Cinzia; De Amicis, Francesca; Lanzino, Marilena; Andò, Sebastiano

    2016-01-01

    Extensive research over the past several decades has identified numerous dietary and phytochemical compounds that have chemopreventive potential and could represent an important source of anti-cancer lead molecules. In this scenario several nutritional factors have attracted considerable attention as modifiable risk factor in the prevention of breast cancer, the most frequently diagnosed cancer and a major cause of death among women worldwide. There is an immediate need for more effective and less toxic therapeutic and preventive strategies for breast cancers able also to counteract the recurrent phenomenon of resistance to hormonal and targeted therapy that represent the first-line treatment in the management of breast cancer patients. The present review focuses on chemopreventive and anti-cancer activities of different bioactive compounds obtained from dietary sources such as Omega-3 fatty acids, naturally present in fish, Resveratrol (3,5,40-trihydroxy-transstilbene), a phytoalexin found in grapes and Epigallocatechin Gallate, a polyphenolic compound found in green tea, or purified from medicinal plant (Oldenlandia Diffusa) and fruits (Ziziphus Jujube) highlighting their potential use in breast cancer treatment. Herein, we discuss the molecular mechanisms by which the bioactive compounds can inhibit carcinogenesis by regulating antioxidant enzyme activities, and inducing antiproliferative and apoptotic effects in different breast cancer cell lines. Understanding the mechanism of action of dietary compounds or traditionally used herbs having potential preventive and therapeutic effects on cancer may provide a rationale for further translational studies. This review emphasizes the importance, in the next future, of a proper scientific validation of these natural bioactive compounds for clinical use in the therapeutic portfolio for breast cancer. PMID:26156544

  16. Indolyl-3-ethanone-α-thioethers: A promising new class of non-toxic antimalarial agents.

    PubMed

    Svogie, Archibald L; Isaacs, Michelle; Hoppe, Heinrich C; Khanye, Setshaba D; Veale, Clinton G L

    2016-05-23

    The success of chemotherapeutics in easing the burden of malaria is under continuous threat from ever-evolving parasite resistance, including resistance to artemisinin combination therapies. Therefore, the discovery of new classes of antimalarials which inhibit new biological targets is imperative to controlling malaria. Accordingly, we report here the discovery of indolyl-3-ethanone-α-thioethers, a new class of antimalarial compounds with encouraging activity. Synthesis of a focused library of compounds revealed important insight into the SAR of this class of compounds, including critical information regarding the position and chemical nature of substituents on both the thiophenol and indole rings. This investigation ultimately led to the discovery of two hit compounds (16 and 27) which exhibited nano molar in vitro antimalarial activity coupled to no observable toxicity against a HeLa cell line. PMID:26974377

  17. 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

  18. 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 ...

  19. 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.

  20. VIEW SHOWING WEST ELEVATION, EAST SIDE OF MEYER AVENUE. SHOWS ...

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

    VIEW SHOWING WEST ELEVATION, EAST SIDE OF MEYER AVENUE. SHOWS 499-501, MUNOZ HOUSE (AZ-73-37) ON FAR RIGHT - Antonio Bustamente House, 485-489 South Meyer Avenue & 186 West Kennedy Street, Tucson, Pima County, AZ

  1. 15. Detail showing lower chord pinconnected to vertical member, showing ...

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

    15. Detail showing lower chord pin-connected to vertical member, showing floor beam riveted to extension of vertical member below pin-connection, and showing brackets supporting cantilevered sidewalk. View to southwest. - Selby Avenue Bridge, Spanning Short Line Railways track at Selby Avenue between Hamline & Snelling Avenues, Saint Paul, Ramsey County, MN

  2. [Absorbable coronary stents. New promising technology].

    PubMed

    Erbel, Raimund; Böse, Dirk; Haude, Michael; Kordish, Igor; Churzidze, Sofia; Malyar, Nasser; Konorza, Thomas; Sack, Stefan

    2007-06-01

    Coronary stent implantation started in Germany 20 years ago. In the beginning, the progress was very slow and accelerated 10 years later. Meanwhile, coronary stent implantation is a standard procedure in interventional cardiology. From the beginning of permanent stent implantation, research started to provide temporary stenting of coronary arteries, first with catheter-based systems, later with stent-alone technology. Stents were produced from polymers or metal. The first polymer stent implantation failed except the Igaki-Tamai stent in Japan. Newly developed absorbable polymer stents seem to be very promising, as intravascular ultrasound (IVUS) and optical coherence tomography have demonstrated. Temporary metal stents were developed based on iron and magnesium. Currently, the iron stent is tested in peripheral arteries. The absorbable magnesium stent (Biotronik, Berlin, Germany) was tested in peripheral arteries below the knee and meanwhile in the multicenter international PROGRESS-AMS (Clinical Performance and Angiographic Results of Coronary Stenting with Absorbable Metal Stents) study. The first magnesium stent implantation was performed on July 30, 2004 after extended experimental testing in Essen. The magnesium stent behaved like a bare-metal stent with low recoil of 5-7%. The stent struts were absorbed when tested with IVUS. Stent struts were not visible by fluoroscopy or computed tomography (CT) as well as magnetic resonance imaging (MRI). That means, that the magnesium stent is invisible and therefore CT and MRI can be used for imaging of interventions. Only using micro-CT the stent struts were visible. The absorption process could be demonstrated in a patient 18 days after implantation due to suspected acute coronary syndrome, which was excluded. IVUS showed a nice open lumen. Stent struts were no longer visible, but replaced by tissue indicating the previous stent location. Coronary angiography after 4 months showed an ischemia-driven target lesion

  3. 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

  4. Gold nanoparticles as novel agents for cancer therapy.

    PubMed

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

    2012-02-01

    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

  5. 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.

  6. Indole alkaloid marine natural products: An established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases

    PubMed Central

    Gul, Waseem; Hamann, Mark T.

    2016-01-01

    The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets. Historically marine natural products have largely been explored as anticancer agents. The indole alkaloids are a class of marine natural products that show unique promise in the development of new drug leads. This report reviews the literature on indole alkaloids of marine origin and also highlights our own research. Specific biological activities of indole alkaloids presented here include: cytotoxicity, antiviral, antiparasitic, anti-inflammatory, serotonin antagonism, Ca-releasing, calmodulin antagonism, and other pharmacological activities. PMID:16236327

  7. Melanoma Vaccines: Mixed Past, Promising Future

    PubMed Central

    Ozao-Choy, Junko; Lee, Delphine J.; Faries, Mark B.

    2014-01-01

    Synopsis Cancer vaccines were one of the earliest forms of immunotherapy to be investigated. Past attempts to vaccinate against cancer, including melanoma, have mixed results, revealing the complexity of what was thought to be a simple concept. However, several recent successes and the combination of improved knowledge of tumor immunology and the advent of new immunomodulators make vaccination a promising strategy for the future. PMID:25245965

  8. 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

  9. 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

    2015-01-01

    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. PMID:26007181

  10. 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., Jr.; 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.

  11. 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.

  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. Natural antioxidants and hypertension: promise and challenges.

    PubMed

    Kizhakekuttu, Tinoy J; Widlansky, Michael E

    2010-08-01

    Hypertension reigns as a leading cause of cardiovascular morbidity and mortality worldwide. Excessive reactive oxygen species (ROS) have emerged as a central common pathway by which disparate influences may induce and exacerbate hypertension. Potential sources of excessive ROS in hypertension include nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mitochondria, xanthine oxidase, endothelium-derived NO synthase, 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), and (4) inefficiency of nonspecific 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 interindividual differences in therapeutic efficacy preclude us from recommending any specific natural antioxidant for antihypertensive therapy at this time. This review focuses on recent literature evaluating naturally occurring antioxidants with respect to their impact on hypertension. PMID:20370791

  14. 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

  15. 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

  16. Inhibition of pyrite oxidation by surface coating agents: Batch and field studies

    NASA Astrophysics Data System (ADS)

    Choi, Jaeyoung; Do Gee, Eun; Yun, Hyun-Shik; Ram Lee, Woo; Park, Young-Tae

    2013-04-01

    The potential of several surface coating agents to inhibit the oxidation of metal sulfide minerals from Young-Dong coal mine and the Il-Gwang gold mine was examined by conducting laboratory scale 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). For the observed time period (8 days), Young-Dong coal mine samples exhibited the least sulfate (SO42-) production in the presence of KMnO4 (16%) or cement (4%) while, for Il-Gwang mine samples, the least SO42- production was observed in presence of KH2PO4 (8%) or cement (2%) compared to control. Field-scale pilot tests at the Il-Gwang site also showed that addition of KH2PO4 decreased SO42- production from 200 to 13 mg L-1 and it also reduced Cu and Mn from 8 and 3 mg L-1, respectively to <0.05 mg L-1 (below ICP-OES detection limits). The experimental results suggested that the use of surface coating agents is a promising alternative for sulfide oxidation inhibition at acid mine drainage sites.

  17. Inhibition of sulfide mineral oxidation by surface coating agents: batch and field studies.

    PubMed

    Ji, Min-Kyu; Gee, Eun-Do; Yun, Hyun-Shik; Lee, Woo-Ram; Park, Young-Tae; Khan, Moonis Ali; Jeon, Byong-Hun; Choi, Jaeyoung

    2012-08-30

    The potential of several surface coating agents to inhibit the oxidation of metal sulfide minerals from Young-Dong coal mine and the Il-Gwang gold mine was examined by conducting laboratory scale 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 (KH(2)PO(4), MgO and KMnO(4) as chemical agents, and apatite, cement and manganite as mineral agents) and incubated with oxidizing agents (H(2)O(2) or NaClO). For the observed time period (8 days), Young-Dong coal mine samples exhibited the least sulfate (SO(4)(2-)) production in the presence of KMnO(4) (16%) or cement (4%) while, for Il-Gwang mine samples, the least SO(4)(2-) production was observed in presence of KH(2)PO(4) (8%) or cement (2%) compared to control. Field-scale pilot tests at the Il-Gwang site also showed that addition of KH(2)PO(4) decreased SO(4)(2-) production from 200 to 13 mg L(-1) and it also reduced Cu and Mn from 8 and 3 mg L(-1), respectively to <0.05 mg L(-1) (below ICP-OES detection limits). The experimental results suggested that the use of surface coating agents is a promising alternative for sulfide oxidation inhibition at acid mine drainage sites. PMID:22727481

  18. 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

  19. 76 FR 55889 - Reopening Notice: Promise Neighborhoods Program-Implementation Grant Competition; Promise...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ..., flooding, property damage, and loss of electrical power that occurred as a result of Hurricane Irene on the... 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...

  20. Can patients with metastatic breast cancer be cured after introduction of newer and more effective agents?

    PubMed

    Ohno, Shinji; Tanaka, Kimihiro; Koga, Chinami; Nishimura, Sumiko; Yamaguchi, Hiroshi; Kawaguchi, Hidetoshi; Yoshiyama, Tomoyuki; Nakamura, Yoshiaki

    2012-07-01

    Unlike early stage breast cancer, metastatic breast cancer (MBC) is generally considered incurable except for a small number of patients with oligometastatic disease. The goal of treatment of MBC should be the prolongation of life and improvement of symptoms and quality of life. The prognoses of patients with MBC, however, have been improved with the introduction of newer, more effective agents. Therefore, the clinical question arises whether MBC patients can be cured with these new therapeutic agents. However, there are a couple of problems in tackling this question, including the duration of follow-up and the presence of strong adjuvant therapy. Firstly, most trials in MBC have a relatively short follow-up; long-term surveillance (>3-5 years) is exceptional, so little is known about the definitive outcome and the exact proportion of long-term survivors. Secondly, most of the patients have received pre- or postoperative adjuvant therapy. The cancer cells at metastatic sites are considered to be relatively resistant to the agents used in metastatic settings. Promisingly, a number of novel therapeutic agents including antibody-drug conjugates, irreversible small molecule HER2-tyrosine inhibitors, and HER2 dimerization inhibitors show promise in the treatment of HER2-overexpressing MBC, as well as PARP-1 [poly(ADP-ribose) polymerase-1] inhibitors for triple-negative breast cancer. PMID:21630056

  1. Branding: a promise with a solid base.

    PubMed

    Emswiller, T; Marosits, M

    1998-01-01

    Over the past several decades, branding as a process of differentiating one company, product, or service from another has been central to the business efforts of a wide range of commercial enterprises. In more recent years, branding has become part of the lexicon of health care, where its function is accepted and its potential benefits desired. Much of the emphasis regarding brand building, however, is in the area of marketing. Although communications and their inherent promises remain an essential component in brand development for health care providers and managed care companies, the ultimate value of branding lies in its integration into an organization's operational structure and strategies. PMID:10185774

  2. Some promising dimensions for behavioral community technology

    PubMed Central

    Fawcett, Stephen B.; Mathews, R. Mark; Fletcher, R. Kay

    1980-01-01

    In recent years, the search for effective and replicable approaches to planned change in communities has escalated. Applied behavior analysts have participated in these efforts to remedy existing community problems and to increase the capacities of community residents to meet their goals. Examples of behavioral technologies for community settings are described and their advantages are noted. Criteria for more contextually appropriate community technologies are suggested and strategies for developing behavioral methods according to these criteria are described. This paper outlines some promising dimensions for behavioral community technology and discusses several possible limitations to a behavioral approach to addressing societal problems. PMID:16795630

  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. 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

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

    PubMed

    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

  6. 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.

  7. Planning a Successful Tech Show

    ERIC Educational Resources Information Center

    Nikirk, Martin

    2011-01-01

    Tech shows are a great way to introduce prospective students, parents, and local business and industry to a technology and engineering or career and technical education program. In addition to showcasing instructional programs, a tech show allows students to demonstrate their professionalism and skills, practice public presentations, and interact…

  8. Hey Teacher, Your Personality's Showing!

    ERIC Educational Resources Information Center

    Paulsen, James R.

    1977-01-01

    A study of 30 fourth, fifth, and sixth grade teachers and 300 of their students showed that a teacher's age, sex, and years of experience did not relate to students' mathematics achievement, but that more effective teachers showed greater "freedom from defensive behavior" than did less effective teachers. (DT)

  9. 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 ...

  10. Nanotechnology: Promises and challenges for tomorrow

    SciTech Connect

    ROMIG JR.,ALTON D.; MICHAEL,JOSEPH R.; MICHALSKE,TERRY A.

    2000-02-29

    Nanotechnology is based on the ability to create and utilize materials, devices and systems through control of the matter at the nanometer scale. If successful, nanotechnology is expected to lead to broad new technological developments. The efficiency of energy conversion can be increased through the use of nanostructured materials with enhanced magnetic, light emission or wear resistant properties. Energy generation using nanostructured photovoltaics or nanocluster driven photocatalysis could fundamentally change the economic viability of renewable energy sources. In addition, the ability to imitate molecular processes found in living organisms may be key to developing highly sensitive and discriminating chemical and biological sensors. Such sensors could greatly expand the range of medical home testing as well as provide new technologies to counter the spread of chemical and biological weapons. Even the production of chemicals and materials could be revolutionized through the development of molecular reactors that can promote low energy chemical pathways for materials synthesis. Although nanotechnologies hold great promise, significant scientific challenges must be addressed before they can convert that promise into a reality. A key challenge in nanoscience is to understand how nano-scale tailoring of materials can lead to novel and enhanced functions. The authors' laboratory, for example, is currently making broad contributions in this area by synthesizing and exploring nanomaterials ranging from layered structures for electronics/photonics to novel nanocrystalline catalysts. They are even adapting functions from biological molecules to synthesize new forms of nanostructured materials.

  11. Carbazole derivatives: a promising scenario for breast cancer treatment.

    PubMed

    Caruso, Anna; Iacopetta, Domenico; Puoci, Francesco; Cappello, Anna Rita; Saturnino, Carmela; Sinicropi, Maria Stefania

    2016-01-01

    Chemotherapeutics used in cancer treatment may elicit pleiotropic effects interfering, for instance, directly on DNA metabolism or on endoplasmic organelles functions. Recently there has been a trend towards the use of molecular-targeted therapies as alternative treatments of cancer, arising from the need to overcome the onset of undesired side effects or drug-resistance. Thus, a major challenge is the design and synthesis of new agents able to interact with specific cellular components, often over-expressed or altered in cancerous cells, such as telomerase and topoisomerase or protein kinases, with reduced toxicity at effective doses. The main molecular targets for the development of new anticancer drugs include: cell surface receptors, signal transduction pathways, enzymes, gene transcription, ubiquitin-proteasome/heat shock proteins, and anti-angiogenic agents. Several natural or synthetic polycyclic molecules with carbazolic nucleus, which show attractive drug-like properties, were identified with the aim to increase their biological activities and their specificity, obtaining cytotoxic agents effective in a panel of cancer cell lines. The cytotoxic profile of these compounds has been assessed using several in vitro assays as, for instance, MTT, colony formation, and flow cytometry assays and some of these compounds showed an interesting profile at sub-micromolar concentrations. The usefulness of some carbazole derivatives has been demonstrated, as well, in preclinical studies. PMID:26156543

  12. [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. PMID:25817449

  13. 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.

  14. 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…

  15. 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.

  16. 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.

  17. Steroidal Ammonium Compounds as New Neuromuscular Blocking Agents.

    PubMed

    Rao, Zhigang; Hu, Hao; Tang, Jiazhi; Liu, Zhiying; Yang, Yue; Qiu, Guofu; Xiao, Yuling; Liu, Peng; Hu, Xianming; Zhou, Xiaoju; Hong, Xuechuan

    2016-05-01

    Neuromuscular blocking agents are widely used as an anesthesia auxiliary in surgery, which induce relaxation of skeletal muscles by blocking signal transmission at the neuromuscular junction. Many neuromuscular blocking agents s were developed over the past decades, but none of them fully meets the needs of the clinic by various reasons. In this study, a series of quaternary ammonium steroidal neuromuscular blocking agents were synthesized and evaluated on isolated mouse phrenic nerve-hemidiaphragms for their bioactivities. The initial separation of mono- and bis-quaternary ammonium compounds turned out to be very challenging on regular silica gel chromatography. Therefore, a facile purification method, in which the silica gel was pretreated with methanolic sodium bromide solution, was finally achieved. Compounds 3g (0.36 μm) and 4g (0.37 μm) exhibited excellent neuromuscular blocking activities, which were about sixfold to sevenfold higher in potency than that of rocuronium (2.50 μm). In addition, other bis-quaternized compounds also showed good potencies close to that of rocuronium. Furthermore, the preliminary structure-activity relationship of this series was also elucidated. Benzyl group was found to be a promising quaternary group in this series. PMID:26684806

  18. 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

  19. 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.

  20. 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. ...

  1. 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.

  2. 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. PMID:26561063

  3. 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

  4. Monoclonal antibodies: the promise and the reality.

    PubMed

    Coons, T

    1995-01-01

    Monoclonal antibodies, or "MoAbs," have revolutionized clinical approaches to diagnostic imaging and therapy of many diseases. The use of MoAbs for diagnosing and treating cancer has been especially promising. However, the full potential of these "magic bullets" has yet to be realized. This article examines the current and potential uses of MoAbs, describes problems with the technology and looks at potential solutions. Along with descriptions of how MoAbs are made and prepared for use in the clinic, the article provides examples of the ways in which MoAbs can be used to complement and expand the information obtained from standard diagnostic imaging modalities. Specific examples of the use of monoclonal antibodies for treating cancer and other diseases also are provided. PMID:7491408

  5. 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.

  6. Promising treatments of tomorrow for multiple sclerosis

    PubMed Central

    Harrison, Daniel M.; Calabresi, Peter A.

    2009-01-01

    The therapeutic options for multiple sclerosis are rapidly expanding. What was once seen as a disease with little hope for treatment is now a target of rapid drug development. Current therapies have demonstrated efficacy in limiting the impact of the disease, but none is fully effective in all patients. However, promising new treatments are on the horizon. In this review we will discuss potential novel immunomodulating drugs that are in advanced stages of investigation; these drugs include monoclonal antibodies, chimeric molecules, and oral therapies. The use of hematopoietic stem cells will also be discussed and, in addition, we will look farther ahead at possible novel targets for the development of new immunomodulatory or neuroprotective pharmaceuticals. PMID:20182576

  7. Prenatal pharmacogenomics: a promising area for research.

    PubMed

    Dorfman, E H; Cheng, E Y; Hebert, M F; Thummel, K E; Burke, W

    2016-08-01

    Clinical applications of prenatal genetic screening currently focus on detection of aneuploidy and other genetic diseases in the developing fetus. Growing evidence suggests that the fetal genome may also be informative about fetal exposures through contributions to placental transport as well as placental and fetal metabolism. Possible clinical applications of prenatal pharmacogenomic screening include prospective optimization of medication selection and dosage, as well as retrospective assessment of whether a fetus was previously exposed to significant risk. Newly available noninvasive methods of prenatal genetic screening mean that relevant fetal genotypes could be made available to obstetricians for use in management of a current pregnancy. This promising area for research merits more attention than it has thus far received.The Pharmacogenomics Journal advance online publication, 10 May 2016; doi:10.1038/tpj.2016.33. PMID:27168097

  8. The Promise of Preventive Cancer Vaccines

    PubMed Central

    Lollini, Pier-Luigi; Cavallo, Federica; Nanni, Patrizia; Quaglino, Elena

    2015-01-01

    Years of unsuccessful attempts at fighting established tumors with vaccines have taught us all that they are only able to truly impact patient survival when used in a preventive setting, as would normally be the case for traditional vaccines against infectious diseases. While true primary cancer prevention is still but a long-term goal, secondary and tertiary prevention are already in the clinic and providing encouraging results. A combination of immunopreventive cancer strategies and recently approved checkpoint inhibitors is a further promise of forthcoming successful cancer disease control, but prevention will require a considerable reduction of currently reported toxicities. These considerations summed with the increased understanding of tumor antigens allow space for an optimistic view of the future. PMID:26343198

  9. 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

  10. 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

  11. Indoles - A promising scaffold for drug development.

    PubMed

    Sravanthi, T V; Manju, S L

    2016-08-25

    Generally, heterocycles occupy a prominent place in chemistry due to their wide range of applications in the fields of drug design, photochemistry, agrochemicals, dyes and so on. Among them, indole scaffolds have been found in most of the important synthetic drug molecules and paved a faithful way to develop effective targets. Privileged structures bind to multiple receptors with high affinity, thus aiding the development of novel biologically active compounds. Among the indole class of compounds, 2-arylindoles appear to be a most promising lead for drug development. The derivatives of 2-arylindoles exhibits antibacterial, anticancer, anti-oxidants, anti-inflammatory, anti-diabetic, antiviral, antiproliferative, antituberculosis activity, etc. This article would provide a clear knowledge on the wide-ranging biological activities of 2-arylindoles over the past two decades, which would be beneficial for the designing of more potent drug targets in order to compete with the existing drugs. PMID:27237590

  12. 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

  13. 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.

  14. Epigenetic Pathways of Oncogenic Viruses: Therapeutic Promises.

    PubMed

    El-Araby, Amr M; Fouad, Abdelrahman A; Hanbal, Amr M; Abdelwahab, Sara M; Qassem, Omar M; El-Araby, Moustafa E

    2016-02-01

    Cancerous transformation comprises different events that are both genetic and epigenetic. The ultimate goal for such events is to maintain cell survival and proliferation. This transformation occurs as a consequence of different features such as environmental and genetic factors, as well as some types of infection. Many viral infections are considered to be causative agents of a number of different malignancies. To convert normal cells into cancerous cells, oncogenic viruses must function at the epigenetic level to communicate with their host cells. Oncogenic viruses encode certain epigenetic factors that lead to the immortality and proliferation of infected cells. The epigenetic effectors produced by oncogenic viruses constitute appealing targets to prevent and treat malignant diseases caused by these viruses. In this review, we highlight the importance of epigenetic reprogramming for virus-induced oncogenesis, with special emphasis on viral epigenetic oncoproteins as therapeutic targets. The discovery of molecular components that target epigenetic pathways, especially viral factors, is also discussed. PMID:26754591

  15. Capecitabine: fulfilling the promise of oral chemotherapy.

    PubMed

    Hwang, Jimmy J; Marshall, John L

    2002-06-01

    Capecitabine is a synthetic oral fluoropyrimidine carbamate that is sequentially activated in a three-step process, which results in the preferential production of 5-fluorouracil in tumours, rather than in the normal surrounding tissue. Capecitabine is proven to be as effective as the combination of 5-fluorouracil and leucovorin administered on the Mayo clinic schedule in patients with metastatic colorectal cancer. It has also been proven to be effective in patients with metastatic breast cancer that has progressed despite prior anthracyclines and taxoids. More recently, it has also been shown to increase survival in combination with docetaxel in patients with metastatic breast cancer in comparison to docetaxel alone. This article reviews the pharmacology and clinical activity of capecitabine, as well as combinations of capecitabine with other chemotherapeutic agents and future directions of investigation with this convenient and widely active antitumour therapy. PMID:12036413

  16. 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

  17. 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

  18. Creating Slide Show Book Reports.

    ERIC Educational Resources Information Center

    Taylor, Harriet G.; Stuhlmann, Janice M.

    1995-01-01

    Describes the use of "Kid Pix 2" software by fourth grade students to develop slide-show book reports. Highlights include collaboration with education majors from Louisiana State University, changes in attitudes of the education major students and elementary students, and problems with navigation and disk space. (LRW)

  19. Producing Talent and Variety Shows.

    ERIC Educational Resources Information Center

    Szabo, Chuck

    1995-01-01

    Identifies key aspects of producing talent shows and outlines helpful hints for avoiding pitfalls and ensuring a smooth production. Presents suggestions concerning publicity, scheduling, and support personnel. Describes types of acts along with special needs and problems specific to each act. Includes a list of resources. (MJP)

  20. Bedaquiline for the treatment of resistant tuberculosis: promises and pitfalls.

    PubMed

    Kakkar, Ashish Kumar; Dahiya, Neha

    2014-07-01

    Treatment of multidrug-resistant tuberculosis (MDR-TB) is hindered by limited efficacy and significant toxicity of second-line drugs. The need for new therapeutic options is critical to combat the global MDR-TB epidemic. Bedaquiline is a novel oral diarylquinoline approved by Food and Drug administration (FDA) for the treatment of adults with pulmonary MDR-TB on the basis of Phase IIb trial data under the provisions of the accelerated approval regulations for serious or life-threatening conditions. The FDA advisory committee members voted unanimously on efficacy data based on surrogate measures, however they were split on the issues of safety of bedaquiline. Main safety concerns include QT interval prolongation, hepatic related adverse events, and excess mortality in bedaquiline treated patients. While bedaquiline approval is a story of many firsts and certainly a welcome addition to the existing arsenal of anti-TB agents, a cautiously optimistic approach is required to assess the risk benefit profile of the drug. Acceleration of further Phase III trials and clinical studies is imperative, as is timely analysis of emerging data on the real world use of the drug. This mini review outlines the clinical pharmacology of bedaquiline highlighting the potential promises and challenges that implicate the risk benefit profile of drug. PMID:24841672

  1. 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

  2. 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. PMID:25549588

  3. 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

  4. Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

    PubMed Central

    Grant, Igor; Cahn, B. Rael

    2008-01-01

    The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control. PMID:18806886

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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…

  10. 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…

  11. 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…

  12. Cancer chemoprevention by garlic and its organosulfur compounds-panacea or promise?

    PubMed

    Nagini, Siddavaram

    2008-04-01

    Of late medicinal plants and functional foods rich in bioactive phytochemicals have received growing attention as potential agents for cancer chemoprevention. Accumulating evidence from epidemiological studies as well as laboratory data supports the anticancer properties of garlic widely used as a medicinal herb and spice. Garlic and its organosulfur compounds (OSCs) appear to exert their anticarcinogenic effects through multiple mechanisms that include modulation of carcinogen metabolism, inhibition of DNA adduct formation, upregulation of antioxidant defences and DNA repair systems, and suppression of cell proliferation by blocking cell cycle progression and/or inducing apoptosis. Since multiple signaling pathways are dysfunctional in cancer and new oncogenic mutations accumulate with carcinogenic progression, dietary agents such as garlic with its rich array of bioactive OSCs that modulate cancer cascades offer promise as potential chemopreventive and chemotherapeutic agents. PMID:18393790

  13. Antibody-Based Biologics and Their Promise to Combat Staphylococcus aureus Infections.

    PubMed

    Sause, William E; Buckley, Peter T; Strohl, William R; Lynch, A Simon; Torres, Victor J

    2016-03-01

    The growing incidence of serious infections mediated by methicillin-resistant Staphylococcus aureus (MRSA) strains poses a significant risk to public health. This risk is exacerbated by a prolonged void in the discovery and development of truly novel antibiotics and the absence of a vaccine. These gaps have created renewed interest in the use of biologics in the prevention and treatment of serious staphylococcal infections. In this review, we focus on efforts towards the discovery and development of antibody-based biologic agents and their potential as clinical agents in the management of serious S. aureus infections. Recent promising data for monoclonal antibodies (mAbs) targeting anthrax and Ebola highlight the potential of antibody-based biologics as therapeutic agents for serious infections. PMID:26719219

  14. "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

  15. ENVITEC shows off air technologies

    SciTech Connect

    McIlvaine, R.W.

    1995-08-01

    The ENVITEC International Trade Fair for Environmental Protection and Waste Management Technologies, held in June in Duesseldorf, Germany, is the largest air pollution exhibition in the world and may be the largest environmental technology show overall. Visitors saw thousands of environmental solutions from 1,318 companies representing 29 countries and occupying roughly 43,000 square meters of exhibit space. Many innovations were displayed under the category, ``thermal treatment of air pollutants.`` New technologies include the following: regenerative thermal oxidizers; wet systems for removing pollutants; biological scrubbers;electrostatic precipitators; selective adsorption systems; activated-coke adsorbers; optimization of scrubber systems; and air pollution monitors.

  16. The Renewed Promise of Medical Informatics.

    PubMed

    van Bemmel, J H; McCray, A T

    2016-01-01

    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. PMID:27199195

  17. 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

  18. 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

  19. 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

  20. Tutorial on agent-based modeling and simulation. Part 2 : how to model with agents.

    SciTech Connect

    Macal, C. M.; North, M. J.; Decision and Information Sciences

    2006-01-01

    Agent-based modeling and simulation (ABMS) is a new approach to modeling systems comprised of interacting autonomous agents. ABMS promises to have far-reaching effects on the way that businesses use computers to support decision-making and researchers use electronic laboratories to do research. Some have gone so far as to contend that ABMS is a new way of doing science. Computational advances make possible a growing number of agent-based applications across many fields. Applications range from modeling agent behavior in the stock market and supply chains, to predicting the spread of epidemics and the threat of bio-warfare, from modeling the growth and decline of ancient civilizations to modeling the complexities of the human immune system, and many more. This tutorial describes the foundations of ABMS, identifies ABMS toolkits and development methods illustrated through a supply chain example, and provides thoughts on the appropriate contexts for ABMS versus conventional modeling techniques.

  1. Pinning synchronization of a mobile agent network

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Sun, You-xian

    2009-11-01

    We investigate the problem of controlling a group of mobile agents in a plane in order to move them towards a desired orbit via pinning control, in which each agent is associated with a chaotic oscillator coupled with those of neighboring agents, and the pinning strategy is to have the common linear feedback acting on a small fraction of agents by random selection. We explore the effects of the pinning probability, feedback gains and agent density in the pinning synchronization of a mobile agent network under a fast-switching constraint, and perform numerical simulations for validation. In particular, we show that there exists a critical pinning density for network synchronization with an unbounded region: above the threshold, the dynamical network can be controlled by pinning; below it, anarchy prevails. And for the network with a single bounded synchronization region, pinning control has little effect as regards enhancing network synchronizability.

  2. 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.

  3. 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.

  4. Oncolytic Bluetongue Viruses: Promise, Progress, and Perspectives

    PubMed Central

    Li, Joseph K.-K.

    2011-01-01

    Humans are sero-negative toward bluetongue viruses (BTVs) since BTVs do not infect normal human cells. Infection and selective degradation of several human cancer cell lines but not normal ones by five US BTV serotypes have been investigated. We determined the susceptibilities of many normal and human cancer cells to BTV infections and made comparative kinetic analyses of their cytopathic effects, survival rates, ultra-structural changes, cellular apoptosis and necrosis, cell cycle arrest, cytokine profiles, viral genome, mRNAs, and progeny titers. The wild-type US BTVs, without any genetic modifications, could preferentially infect and degrade several types of human cancer cells but not normal cells. Their selective and preferential BTV-degradation of human cancer cells is viral dose–dependent, leading to effective viral replication, and induced apoptosis. Xenograft tumors in mice were substantially reduced by a single intratumoral BTV injection in initial in vivo experiments. Thus, wild-type BTVs, without genetic modifications, have oncolytic potentials. They represent an attractive, next generation of oncolytic viral approach for potential human cancer therapy combined with current anti-cancer agents and irradiation. PMID:21747785

  5. 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

  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. Tumor Characterization with Dynamic Contrast Enhanced Magnetic Resonance Imaging and Biodegradable Macromolecular Contrast Agents in Mice

    PubMed Central

    Wu, Xueming; Feng, Yi; Jeong, Eun-Kee; Emerson, Lyska; Lu, Zheng-Rong

    2009-01-01

    Purpose To investigate the efficacy of polydisulfide-based biodegradable macromolecular contrast agents of different degradability and molecular weight for tumor characterization based on angiogenesis using dynamic contrast enhanced MRI (DCE-MRI). Methods Biodegradable macromolecular MRI contrast agents, GDCC and GDCP, with molecular weight of 20 and 70 KDa were evaluated for tumor characterization. The DCE-MRI studies were performed in nude mice bearing MDA PCa 2b and PC-3 human prostate tumor xenografts. Tumor angiogenic kinetic parameters, endothelium transfer coefficient (Ktrans) and fractional tumor plasma volume (fPV), were calculated from the DCE-MRI data using a two-compartment model. Results There was no significant difference in the fPV values between two tumor models estimated with the same agent except for GDCC-70. The Ktrans values in both tumor models decreased with increasing molecular weight of the agents. GDCC-70 showed a higher Ktrans values than GDCP-70 due to high degradability of the former in both tumor models (p < 0.05). The Ktrans values of MDA PCa 2b tumors were significantly higher than those of PC-3 tumors estimated by Gd(DTPA-BMA), GDCC-20, GDCC-70, GDCP-70, and albumin-(Gd-DTPA) (p < 0.05). Conclusions The polydisulfide based biodegradable macromolecular MRI contrast agents are promising in tumor characterization with dynamic contrast enhanced MRI. PMID:19597972

  8. 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

  9. 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.

  10. Chemical crowd control agents.

    PubMed

    Menezes, Ritesh G; Hussain, Syed Ather; Rameez, Mansoor Ali Merchant; Kharoshah, Magdy A; Madadin, Mohammed; Anwar, Naureen; Senthilkumaran, Subramanian

    2016-03-01

    Chemical crowd control agents are also referred to as riot control agents and are mainly used by civil authorities and government agencies to curtail civil disobedience gatherings or processions by large crowds. Common riot control agents used to disperse large numbers of individuals into smaller, less destructive, and more easily controllable numbers include chloroacetophenone, chlorobenzylidenemalononitrile, dibenzoxazepine, diphenylaminearsine, and oleoresin capsicum. In this paper, we discuss the emergency medical care needed by sufferers of acute chemical agent contamination and raise important issues concerning toxicology, safety and health. PMID:26658556

  11. 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

  12. 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

  13. 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

  14. 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. PMID:26877135

  15. Silicene, a promising new 2D material

    NASA Astrophysics Data System (ADS)

    Oughaddou, Hamid; Enriquez, Hanna; Tchalala, Mohammed Rachid; Yildirim, Handan; Mayne, Andrew J.; Bendounan, Azzedine; Dujardin, Gérald; Ait Ali, Mustapha; Kara, Abdelkader

    2015-02-01

    Silicene is emerging as a two-dimensional material with very attractive electronic properties for a wide range of applications; it is a particularly promising material for nano-electronics in silicon-based technology. Over the last decade, the existence and stability of silicene has been the subject of much debate. Theoretical studies were the first to predict a puckered honeycomb structure with electronic properties resembling those of graphene. Though these studies were for free-standing silicene, experimental fabrication of silicene has been achieved so far only through epitaxial growth on crystalline surfaces. Indeed, it was only in 2010 that researchers presented the first experimental evidence of the formation of silicene on Ag(1 1 0) and Ag(1 1 1), which has launched silicene in a similar way to graphene. This very active field has naturally led to the recent growth of silicene on Ir(1 1 1), ZrB2(0 0 0 1) and Au(1 1 0) substrates. However, the electronic properties of epitaxially grown silicene on metal surfaces are influenced by the strong silicene-metal interactions. This has prompted experimental studies of the growth of multi-layer silicene, though the nature of its "silicene" structure remains questionable. Of course, like graphene, synthesizing free-standing silicene represents the ultimate challenge. A first step towards this has been reported recently through chemical exfoliation from calcium disilicide (CaSi2). In this review, we discuss the experimental and theoretical studies of silicene performed to date. Special attention is given to different experimental studies of the electronic properties of silicene on metal substrates. New avenues for the growth of silicene on other substrates with different chemical characteristics are presented along with foreseeable applications such as nano-devices and novel batteries.

  16. 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

  17. 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.

  18. Copper complexes as anticancer agents.

    PubMed

    Marzano, Cristina; Pellei, Maura; Tisato, Francesco; Santini, Carlo

    2009-02-01

    Metal-based antitumor drugs play a relevant role in antiblastic chemotherapy. Cisplatin is regarded as one of the most effective drugs, even if severe toxicities and drug resistance phenomena limit its clinical use. Therefore, in recent years there has been a rapid expansion in research and development of novel metal-based anticancer drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. The variety of metal ion functions in biology has stimulated the development of new metallodrugs other than Pt drugs with the aim to obtain compounds acting via alternative mechanisms of action. Among non-Pt compounds, copper complexes are potentially attractive as anticancer agents. Actually, since many years a lot of researches have actively investigated copper compounds based on the assumption proposal that endogenous metals may be less toxic. It has been established that the properties of copper-coordinated compounds are largely determined by the nature of ligands and donor atoms bound to the metal ion. In this review, the most remarkable achievements in the design and development of copper(I, II) complexes as antitumor agents are discussed. Special emphasis has been focused on the identification of structure-activity relationships for the different classes of copper(I,II) complexes. This work was motivated by the observation that no comprehensive surveys of copper complexes as anticancer agents were available in the literature. Moreover, up to now, despite the enormous efforts in synthesizing different classes of copper complexes, very few data concerning the molecular basis of the mechanisms underlying their antitumor activity are available. This overview, collecting the most significant strategies adopted in the last ten years to design promising anticancer copper(I,II) compounds, would be a help to the researchers working in this field. PMID:19199864

  19. A New Promising Approach of Pattern Scaling

    NASA Astrophysics Data System (ADS)

    Herger, N.; Sanderson, B. M.; Knutti, R.

    2014-12-01

    Running large ensembles of fully coupled climate models is computationally expensive. This is exactly where climate emulators - among which pattern scaling is perhaps the most popular one - come into play.The traditional pattern scaling technique assumes that a normalized fixed spatial pattern of a certain variable of interest can be scaled by the trajectory of the global mean temperature change.Instead of scaling a pattern at a certain period of time from a higher/lower emission scenario, we propose to consider a scaling in time. With this approach, one needs to find a time period with matching global mean surface temperature on an already existing emission pathway. We expect to find the following advantages as compared to the traditional technique:Consistency between variables (e.g. physical relationship between temperature and precipitation) and correlation in space and time is preserved. Variability does not have to be scaled in magnitude, and is consistent with the global temperature change. And finally, physical limits are preserved (e.g. sea ice loss) to the degree that they depend on global temperature. It is currently unknown whether different forcing agents (aerosols, land use change) which differ in magnitude across scenarios might cause a problem with the proposed approach, but the same problems arise with scaling patterns between scenarios at a fixed time.We first test this new approach with one model (CESM) and then with a multi-model ensemble (CMIP5). Due to the interdependency in a multi-model ensemble, we test the sensitivity of our results on the manner the individual models are weighted. In a last step, we aim to consider the effect of forcing, variables (such as climate extreme indices) and model resolution on the viability of the traditional and proposed pattern scaling approaches.

  20. Synthesis, anti-cancer evaluation of benzenesulfonamide derivatives as potent tubulin-targeting agents.

    PubMed

    Yang, Jun; Yang, Simin; Zhou, Shanshan; Lu, Dongbo; Ji, Liyan; Li, Zhongjun; Yu, Siwang; Meng, Xiangbao

    2016-10-21

    A series of benzenesulfonamide derivatives were synthesized and evaluated for their anti-proliferative activity and interaction with tubulin. These new derivatives showed significant activities against cellular proliferative and tubulin polymerization. Compound BA-3b proved to be the most potent compound with IC50 value ranging from 0.007 to 0.036 μM against seven cancer cell lines, and three drug-resistant cancer cell lines, which indicated a promising anti-cancer agent. The target tubulin was also verified by dynamic tubulin polymerization assay and tubulin intensity assay. PMID:27423028

  1. Gd-doped BNNTs as T2-weighted MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Ciofani, Gianni; Boni, Adriano; Calucci, Lucia; Forte, Claudia; Gozzi, Alessandro; Mazzolai, Barbara; Mattoli, Virgilio

    2013-08-01

    This work describes, for the first time, doping of boron nitride nanotubes (BNNTs) with gadolinium (Gd@BNNTs), a stable functionalization that permits non-invasive BNNT tracking via magnetic resonance imaging (MRI). We report the structure, Gd loading, and relaxometric properties in water suspension at 7 T of Gd@BNNTs, and show the behaviour of these nanostructures as promising T2-weighted contrast agents. Finally, we demonstrate their complete biocompatibility in vitro on human neuroblastoma cells, together with their ability to effectively label and affect contrast in MRI images at 7 T.

  2. Identification of novel 2-aminothiazole conjugated nitrofuran as antitubercular and antibacterial agents.

    PubMed

    Ran, Kai; Gao, Chao; Deng, Hongxia; Lei, Qian; You, Xinyu; Wang, Ningyu; Shi, Yaojie; Liu, Zhihao; Wei, Wei; Peng, Cuiting; Xiong, Lu; Xiao, Kunjie; Yu, Luoting

    2016-08-01

    The emergence of antibiotic resistant pathogens is an ongoing main problem in the therapy of bacterial infections. In order to develop promising antitubercular and antibacterial lead compounds, we designed and synthesized a new series of derivatives of 2-aminothiazole conjugated nitrofuran with activities against both Mycobacterium tuberculosis and Staphylococcus aureus. Eight compounds 12e, 12k, 12l, 12m, 18a, 18d, 18e, and 18j emerged as promising antitubercular agents. Structure-activity relationships (SARs) were discussed and showed that the derivatives substituted at the position-3 of benzene of 5-nitro-N-(4-phenylthiazol-2-yl)furan-2-carboxamide exhibited superior potency. The most potent compound 18e, substituted with benzamide at this position, displayed minimum inhibitory concentrations (MICs) of 0.27μg/mL against Mtb H37Ra and 1.36μg/mL against S. aureus. Furthermore, compound 18e had no obvious cytotoxicity to normal Vero cells (IC50=50.2μM). The results suggest that the novel scaffolds of aminothiazole conjugated nitrofuran would be a promising class of potent antitubercular and antimicrobial agents. PMID:27289321

  3. 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…

  4. 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…

  5. 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

  6. 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.

  7. 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

  8. 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

  9. Pediatric Antifungal Agents

    PubMed Central

    Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Smith, P Brian

    2009-01-01

    Purpose of review In immunocompromised hosts, invasive fungal infections are common and fatal. In the past decade, the antifungal armamentarium against invasive mycoses has expanded greatly. The purpose of this report is to review the most recent literature addressing the use of antifungal agents in children. Recent findings Most studies evaluating the safety and efficacy of antifungal agents are limited to adults. However, important progress has been made in describing the pharmacokinetics and safety of newer antifungal agents in children, including the echinocandins. Summary Dosage guidelines for newer antifungal agents are currently based on adult and limited pediatric data. Because important developmental pharmacology changes occur throughout childhood impacting the pharmacokinetics of these agents, antifungal studies specifically designed for children are necessary. PMID:19741525

  10. 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.

  11. 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

  12. 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

  13. Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma.

    PubMed

    Abakumova, Tatiana; Abakumov, Maxim; Shein, Sergey; Chelushkin, Pavel; Bychkov, Dmitry; Mukhin, Vladimir; Yusubalieva, Gaukhar; Grinenko, Nadezhda; Kabanov, Alexander; Nukolova, Natalia; Chekhonin, Vladimir

    2016-01-01

    Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM(-1) s(-1) at 7 T) than the commercial agent Magnevist® (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI. PMID:26265140

  14. 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…

  15. 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.

  16. 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.

  17. 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

  18. 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…

  19. 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…

  20. 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.

  1. Biological agents in management of osteoporosis.

    PubMed

    Tella, Sri Harsha; Gallagher, J Christopher

    2014-11-01

    Osteoporosis is a skeletal disease associated with an imbalance between formation and resorption, leading to net loss of bone mass, loss of bone microarchitecture, and development of fractures. Bone resorption is primarily due to an activation of osteoclastogenesis and an increase in receptor activator of nuclear factor kappa-B ligand (RANKL) expression, a cytokine involved in the final pathway of the osteoclast cycle.Recent studies of genetic diseases led to the discovery of the wingless-type (Wnt) signaling pathway that plays a major role in bone formation. Further work showed that sclerostin produced by osteocytes and the Dickkopf (DKK1) protein secreted in bone were negative regulators of the Wnt signaling bone formation pathway that act directly by binding to the co-receptors LRP5 and LRP6 of WnT and thereby inhibiting the anabolic Wnt pathway. This understanding of the bone remodeling led to the discovery of new biological drugs that target these pathways and have been evaluated in clinical trials.The current article discusses the role of these newer "biological" agents in management of osteoporosis. Denosumab, a human monoclonal antibody that specifically binds RANKL, blocks the binding of RANK to its ligand markedly reducing bone resorption, increases bone density, and reduces fractures and is approved for osteoporosis. Parathyroid hormone PTH 1-34 (teriparatide) stimulates bone formation through inhibition of sclerostin, DKK1, and frizzled protein; increases BMD; improves microarchitecture; and decreases fractures and is approved for osteoporosis. The anti-sclerostin antibodies (romosozumab, blosozumab) increase bone mass by neutralizing the negative effects of sclerostin on the Wnt signaling pathway. These biologics are being evaluated now in a clinical trial and early data looks promising. Cathepsin K is a proteolytic enzyme that degrades bone matrix and inhibitors such as odanacatib show increasing bone density and perhaps decreased fractures. The

  2. 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

  3. 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

  4. Brain nuclear magnetic resonance imaging enhanced by a paramagnetic nitroxide contrast agent: preliminary report. [Dogs

    SciTech Connect

    Brasch, R.C.; Nitecki, D.E.; Brant-Zawadzki, M.; Enzmann, D.R.; Wesbey, G.E.; Tozer, T.N.; Tuck, L.D.; Cann, C.E.; Fike, J.R.; Sheldon, P.

    1983-11-01

    Contrast-enhancing agents for demonstrating abnormalities of the blood-brain barrier may extend the diagnostic utility of proton nuclear magnetic resonance (NMR) imaging. TES, a nitroxide stable free radical derivative, was tested as a central nervous system contrast enhancer in dogs with experimentally induced unilateral cerebritis or radiation cerebral damage. After intravenous injection of TES, the normal brain showed no change in NMR appearance, but areas of disease demonstrated a dramatic increase (up to 45%) in spin-echo intensity and a decrease in T/sub 1/, relaxation times. The areas of disease defined by TES enhancement were either not evident on the nonenhanced NMR images or were better defined after contrast administration. In-depth tests of toxicity, stability, and metabolism of this promising NMR contrast agent are now in progress.

  5. A Recent Perspective on Discovery and Development of Diverse Therapeutic Agents Inspired from Isatin Alkaloids.

    PubMed

    Rane, Rajesh A; Karunanidhi, Sivanandhan; Jain, Kavita; Shaikh, Mahamadhanif; Hampannavar, Girish; Karpoormath, Rajshekhar

    2016-01-01

    Isatin as an alkaloidal framework have consistently attracted attention of medicinal chemist towards development of wide range of novel therapeutic agents. This review report has discussed significant isatin lead molecules and their derivatives which have shown promising biological potential in recent times. The substituted isatins showing a potent pharmacological activities such as antimicrobial, antitubercular, anticancer, antioxidant, anti-histaminic, anti-HIV, antiviral, anti-inflammatory, anti-Parkinson's and antidiabetic have been described in this review. The mechanism of action leading to therapeutic activity of the respective isatin derivation has also been recorded. This review reveals that the systematic and rational modifications on isatin motif exhibited significant bio-activities which can be exploited for the development of potent novel therapeutic agents in the future studies. Hence the quest to investigate more structural alterations on isatin scaffold should be continued. PMID:26369813

  6. 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.

  7. Plant-Derived Urease Inhibitors as Alternative Chemotherapeutic Agents.

    PubMed

    Hassan, Sherif T S; Žemlička, Milan

    2016-07-01

    Inhibition of the metalloenzyme urease has important pharmacologic applications in the field of antiulcer and antigastric cancer agents. Urease is involved in many serious infections caused by Helicobacter pylori in the gastric tract as well as by Proteus and related species in the urinary tract. Although numerous studies have described several novel urease inhibitors (UIs) used for the treatment of gastric and urinary infections, all these compounds have exhibited severe side effects, toxicity, and instability. Therefore, to overcome such problems, it is necessary to search for new sources of UIs, such as natural products, that provide reduced side effects, low toxicity, greater stability, and bioavailability. As limited studies have been conducted on plant-derived UIs, this paper aims to highlight and summarize the most promising compounds isolated and identified from plants, such as terpenoids, phenolic compounds, alkaloids, and other substances with inhibitory activities against plant and bacterial ureases; these are in vitro and in vivo studies with an emphasis on structure-activity relationship studies and types of inhibition that show high and promising levels of anti-urease activity. This will aid medicinal chemists in the design and synthesis of novel and pharmacologically potent UIs useful for the development of antiulcer drugs. PMID:27244041

  8. Identification of thiostrepton as a novel therapeutic agent that targets human colon cancer stem cells

    PubMed Central

    Ju, S-Y; Huang, C-YF; 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

  9. 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

  10. Hydroxyquinoline based binders: promising ligands for chelatotherapy?

    PubMed

    Budimir, Ana; Humbert, Nicholas; Elhabiri, Mourad; Osinska, Iwona; Biruš, Mladen; Albrecht-Gary, Anne-Marie

    2011-03-01

    We report here a thorough physico-chemical study of the coordination properties of clioquinol, an oxine-type active neurological drug in Alzheimer's disease, toward biologically relevant divalent metal ions (Cu, Zn, Ni, Co and Mn). Using a fruitful combination of electrospray mass spectrometry, absorption spectrophotometry and potentiometry, we have characterized the mono- and bis-chelated metal ion species. The determination of the stability constants showed a classical thermodynamic behavior along the studied series with the cupric complexes being by far the most stable species. Our data are discussed within the scope of Alzheimer's disease. PMID:20926137

  11. 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

  12. 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. PMID:20945266

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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 ...

  19. Treatment of irritable bowel syndrome: beyond fiber and antispasmodic agents

    PubMed Central

    Sainsbury, Anita; Ford, Alexander C.

    2011-01-01

    Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract of unknown etiology. The diagnosis of IBS is made clinically, using symptom-based criteria such as the Manning or Rome criteria. Medical therapy for this condition has traditionally been directed towards symptom relief, using fiber or antispasmodic agents. In recent years, emerging data have confirmed the efficacy of antidepressants, psychological therapies, 5-HT3 antagonists, 5-HT4 agonists, and probiotics in the short-term treatment of IBS, although whether these therapies influence the long-term course of the disease is unknown. Increasing knowledge regarding the pathophysiological mechanisms underlying IBS has resulted in a number of novel molecular treatments, which show promise. These include therapies targeting gastrointestinal mucosal chloride channels and guanylate cyclase-C receptors, as well as highly selective agents influencing serotonergic transmission that, at the time of writing, do not appear to have any severe deleterious effects. In this article we provide a summary of current and emerging therapies in this field. PMID:21694813

  20. 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.

  1. Recombinant mumps virus as a cancer therapeutic agent.

    PubMed

    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 21(st) 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

  2. 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

  3. 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

  4. Quinones as mutagens, carcinogens, and anticancer agents: introduction and overview

    SciTech Connect

    Smith, M.T.

    1985-01-01

    Quinones are widespread in the environment, occurring both naturally and as pollutants. Human exposure to them is, therefore, extensive. Quinones also form an important class of toxic metabolites generated as a result of the metabolism of phenols and related compounds, including phenol itself, 1-naphthol, and diethylstilbesterol. The mechanisms by which quinones exert their toxic effects are complex, but two processes appear to be centrally involved: the direct arylation of sulfhydryls, and the generation of active oxygen species via redox cycling. Certain quinones have been shown to be mutagenic via the formation of active oxygen species and others via their conversion to DNA-binding semiquinone free radicals. Paradoxically, quinones are not only mutagenic and therefore potentially carcinogenic, they are also effective anticancer agents. Classic examples are Adriamycin (doxorubicin hydrochloride) and mitomycin C, but other less complex quinones also show effective antitumor activity. The design of novel quinones that are more selective in their toxicity to human tumor cells and whose mechanism of action if understood seems a promising approach in cancer treatment, especially if host toxicity can be prevented via the use of chemoprotective agents.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. A promising parenting intervention in foster care.

    PubMed

    Linares, L Oriana; Montalto, Daniela; Li, MinMin; Oza, Vikash S

    2006-02-01

    The purpose of this study was to evaluate the effectiveness of a 2-component intervention for biological and foster parent (pairs) to improve parenting practices, co-parenting, and child externalizing problems. Participants were biological and foster parents (N=128) of primarily neglected children (ages 3 to 10 years) placed in regular foster homes. Biological and foster parents were randomly assigned in pairs to the intervention (n=80) or a usual care (n=48) condition. Intervention families received a 12-week parenting course (Incredible Years) and a newly developed co-parenting component. Key findings included significant gains in positive parenting and collaborative co-parenting for both biological and foster parents at the end of the intervention. At follow-up, intervention parents sustained greater improvement in positive parenting, showed gains in clear expectations, and reported a trend for fewer child externalizing problems. Findings supported the feasibility of offering joint parenting training to meet the needs of participating families and demonstrated that the co-parenting construct applied to families in the foster care system was amenable to intervention. PMID:16551141

  15. The emergence and promise of functional biogeography

    PubMed Central

    Violle, Cyrille; Reich, Peter B.; Pacala, Stephen W.; Enquist, Brian J.; Kattge, Jens

    2014-01-01

    Understanding, modeling, and predicting the impact of global change on ecosystem functioning across biogeographical gradients can benefit from enhanced capacity to represent biota as a continuous distribution of traits. However, this is a challenge for the field of biogeography historically grounded on the species concept. Here we focus on the newly emergent field of functional biogeography: the study of the geographic distribution of trait diversity across organizational levels. We show how functional biogeography bridges species-based biogeography and earth science to provide ideas and tools to help explain gradients in multifaceted diversity (including species, functional, and phylogenetic diversities), predict ecosystem functioning and services worldwide, and infuse regional and global conservation programs with a functional basis. Although much recent progress has been made possible because of the rising of multiple data streams, new developments in ecoinformatics, and new methodological advances, future directions should provide a theoretical and comprehensive framework for the scaling of biotic interactions across trophic levels and its ecological implications. PMID:25225414

  16. Anticancer agent-based marine natural products and related compounds.

    PubMed

    Chen, Jian-Wei; Wu, Qi-Hao; Rowley, David C; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine natural products constitute a huge reservoir of anticancer agents. Consequently during the past decades, several marine anticancer compounds have been isolated, identified, and approved for anticancer treatment or are under trials. In this article the sources, structure, bioactivities, mode of actions, and analogs of some promising marine and derived anticancer compounds have been discussed. PMID:25559315

  17. House fly management with viral and botanical agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    House flies are major pests of human and animal health throughout the world and are among the most difficult to control because of resistance to every insecticide that has been developed for their control. A promising microbial agent for fly control is salivary gland hypertrophy virus (MdSGHV), a m...

  18. 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. PMID:27306417

  19. 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

  20. 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

  1. Design of a Mobile Agent-Based Adaptive Communication Middleware for Federations of Critical Infrastructure Simulations

    NASA Astrophysics Data System (ADS)

    Görbil, Gökçe; Gelenbe, Erol

    The simulation of critical infrastructures (CI) can involve the use of diverse domain specific simulators that run on geographically distant sites. These diverse simulators must then be coordinated to run concurrently in order to evaluate the performance of critical infrastructures which influence each other, especially in emergency or resource-critical situations. We therefore describe the design of an adaptive communication middleware that provides reliable and real-time one-to-one and group communications for federations of CI simulators over a wide-area network (WAN). The proposed middleware is composed of mobile agent-based peer-to-peer (P2P) overlays, called virtual networks (VNets), to enable resilient, adaptive and real-time communications over unreliable and dynamic physical networks (PNets). The autonomous software agents comprising the communication middleware monitor their performance and the underlying PNet, and dynamically adapt the P2P overlay and migrate over the PNet in order to optimize communications according to the requirements of the federation and the current conditions of the PNet. Reliable communications is provided via redundancy within the communication middleware and intelligent migration of agents over the PNet. The proposed middleware integrates security methods in order to protect the communication infrastructure against attacks and provide privacy and anonymity to the participants of the federation. Experiments with an initial version of the communication middleware over a real-life networking testbed show that promising improvements can be obtained for unicast and group communications via the agent migration capability of our middleware.

  2. 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. PMID:26552963

  3. Biodegradable Iodinated Polydisulfides as Contrast Agents for CT Angiography

    PubMed Central

    Jin, Erlei; Zheng-Rong, Lu

    2014-01-01

    Current clinical CT contrast agents are mainly small molecular iodinated compounds, which often suffer from short blood pool retention for more comprehensive cardiovascular CT imaging and may cause contrast-induced nephropathy. In this work, we prepared polydisulfides containing a traditional iodinated CT contrast agent in order to optimize the pharmacokinetics of the agent and improve its safety. Initially acting as a macromolecular agent and achieving sharp blood vessel delineation, the polydisulfides can be reduced by endogenous thiols via disulfide-thiol exchange reaction to oligomers that can be readily excreted via renal filtration. Short polyethylene glycol (PEG) chain was also introduced to the polymers to further modify the in vivo properties of the agents. Strong and prolonged vascular enhancement has been generated with two new agents in mice (5–10 times higher blood pool enhancement than iodinaxol). The polydisulfide agents gradually degraded and excreted via renal filtration. The gradual excretion process could prevent contrast induced nephropathy. These results suggest that the biodegradable macromolecular CT contrast agents are promising safe and effective blood contrast agents for CT angiography and image-guided interventions. PMID:24768156

  4. Vesicular Stomatitis Virus as an Oncolytic Agent against Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Murphy, Andrea M.; Besmer, Dahlia M.; Moerdyk-Schauwecker, Megan; Moestl, Natascha; Ornelles, David A.; Mukherjee, Pinku

    2012-01-01

    Vesicular stomatitis virus (VSV) is a promising oncolytic agent against a variety of cancers. However, it has never been tested in any pancreatic cancer model. Pancreatic ductal adenocarcinoma (PDA) is the most common and aggressive form of pancreatic cancer. In this study, the oncolytic potentials of several VSV variants were analyzed in a panel of 13 clinically relevant human PDA cell lines and compared to conditionally replicative adenoviruses (CRAds), Sendai virus and respiratory syncytial virus. VSV variants showed oncolytic abilities superior to those of other viruses, and some cell lines that exhibited resistance to other viruses were successfully killed by VSV. However, PDA cells were highly heterogeneous in their susceptibility to virus-induced oncolysis, and several cell lines were resistant to all tested viruses. Resistant cells showed low levels of very early VSV RNA synthesis, indicating possible defects at initial stages of infection. In addition, unlike permissive PDA cell lines, most of the resistant cell lines were able to both produce and respond to interferon, suggesting that intact type I interferon responses contributed to their resistance phenotype. Four cell lines that varied in their permissiveness to VSV-ΔM51 and CRAd dl1520 were tested in mice, and the in vivo results closely mimicked those in vitro. While our results demonstrate that VSV is a promising oncolytic agent against PDA, further studies are needed to better understand the molecular mechanisms of resistance of some PDAs to oncolytic virotherapy. PMID:22238308

  5. 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.

  6. Design and synthesis of 3,5-diarylisoxazole derivatives as novel class of anti-hyperglycemic and lipid lowering agents.

    PubMed

    Kumar, Atul; Maurya, Ram Awatar; Sharma, Siddharth; Ahmad, Pervez; Singh, A B; Tamrakar, A K; Srivastava, Arvind K

    2009-07-15

    We have designed 1,3-disubstituted-5-membered heteroaromatic ring system as a common core motif from known anti-hyperglycemic agents. Designed compounds were synthesized and screened for in vivo anti-hyperglycemic activity in sucrose loaded model (SLM), sucrose-challenged streptozotocin-induced diabetic rat model (STZ-S) as well as db/db mice model. Some of the synthesized compounds showed promising in vivo anti-hyperglycemic as well as moderate lipid lowering activity. Synthesized Compounds were screened in various in vitro models of type-2 diabeties such as DPP-4, PTP1B and PPARgamma to know the mechanism of their anti-hyperglycemic action. None of the synthesized compounds showed DPP-4 inhibitory as well as PPARgamma activity. These compounds have shown promising PTP-1B inhibitory activity there by revealing that compounds exhibit anti-diabetic activity by PTP1B pathway. PMID:19500993

  7. 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.

  8. Incretin agents in type 2 diabetes

    PubMed Central

    Ross, Stuart A.; Ekoé, Jean-Marie

    2010-01-01

    Abstract OBJECTIVE To evaluate the emerging classes of antihyperglycemic agents that target the incretin pathway, including their therapeutic efficacy and side effect profiles, in order to help identify their place among the treatment options for patients with type 2 diabetes. QUALITY OF EVIDENCE MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched. Most evidence is level I and II. MAIN MESSAGE Two classes of incretin agents are currently available: glucagonlike peptide 1 (GLP1) receptor agonists and dipeptidyl peptidase 4 (DPP4) inhibitors, both of which lower hyperglycemia considerably without increasing the risk of hypoglycemia. The GLP1 receptor agonists have a greater effect on patients’ glycated hemoglobin A1c levels and cause sustained weight loss, whereas the DPP4 inhibitors are weight-neutral. CONCLUSION The GLP1 and DPP4 incretin agents, promising and versatile antihyperglycemic agents, are finding their way into the therapeutic algorithm for treating type 2 diabetes. They can be used in patients not adequately controlled by metformin monotherapy or as initial therapy in those for whom metformin is contraindicated. PMID:20631270

  9. Agent Based Modeling Applications for Geosciences

    NASA Astrophysics Data System (ADS)

    Stein, J. S.

    2004-12-01

    a thermodynamic framework as a set of reactions that roll-up the integrated effect that diverse biological communities exert on a geological system. This approach may work well to predict the effect of certain biological communities in specific environments in which experimental data is available. However, it does not further our knowledge of how the geobiological system actually functions on a micro scale. Agent-based techniques may provide a framework to explore the fundamental interactions required to explain the system-wide behavior. This presentation will present a survey of several promising applications of agent-based modeling approaches to problems in the geosciences and describe specific contributions to some of the inherent challenges facing this approach.

  10. Frequently asked questions: iodinated contrast agents.

    PubMed

    Bettmann, Michael A

    2004-10-01

    Although iodinated contrast agents are safe and widely used, adverse events occur and questions remain about their use, safety, and interactions. Some questions are easily answered and others still require extensive investigation. For one frequent question--is informed consent necessary before all contrast media injections--the simple answer is no. Another question concerns use of contrast media in patients with prior reactions or allergies. Contrast agents can be safely used in such patients, but special care must be taken to be aware of what the previous reaction was and to be ready to treat any reaction. The protective role of pre-treatment with steroids is well established for minor reactions, but they may not prevent major reactions. It is important to realize that even life-threatening, anaphylactoid reactions are not the result of a true allergy to contrast media. Many questions arise about contrast agent-induced nephropathy. Baseline serum creatinine values should be obtained in patients who are at risk, not all patients. The incidence and natural history of contrast agent-induced nephropathy remain unclear. It occurs only in patients with compromised renal function before contrast agent injection, but even patients with normal serum creatinine levels can have renal dysfunction. Calculated creatinine clearance is a better way to determine risk and to follow this complication. The outcome in almost all patients is benign, with progression to end-stage renal disease being rare. The major risk factors, in addition to renal dysfunction, are long-standing diabetes mellitus, dehydration, and use of other nephrotoxic medications. Recent work in preventing and ameliorating contrast agent-induced nephropathy with N-acetyl cysteine, substitution of an isosmolal nonionic contrast agent, and various hydration regimens has been promising. Another common concern is use of iodinated contrast agents in pregnant or breast-feeding women. In both cases, there is no evidence

  11. The Antimicrobial Properties of Cedar Leaf (Thuja plicata) Oil; A Safe and Efficient Decontamination Agent for Buildings

    PubMed Central

    Hudson, James; Kuo, Michael; Vimalanathan, Selvarani

    2011-01-01

    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

  12. Discovery of BC-01, a novel mutual prodrug (hybrid drug) of ubenimex and fluorouracil as anticancer agent.

    PubMed

    Jiang, Yuqi; Li, Xiaoyang; Hou, Jinning; Huang, Yongxue; Jia, Yuping; Zou, Mingming; Zhang, Jian; Wang, Xuejian; Xu, Wenfang; Zhang, Yingjie

    2016-10-01

    We designed and synthesized a novel mutual prodrug, named BC-01 (3), by integrating ubenimex and Fluorouracil (5-FU) into one molecule based on prior research results that showed that a combination of the aminopeptidase N (CD13) inhibitor, ubenimex, and the cytotoxic antitumor agent, 5-FU, exhibited improved in vitro and in vivo antitumor efficiency. 3 showed potent inhibitory activity against CD13 enzymatic activity. Compared with ubenimex, 3 exhibited more potent anti-angiogenesis effects, and compared with the approved 5-FU prodrug, capecitabine, 3 exhibited more potent tumor growth inhibitory and anti-metastasis effects. Additionally, compared with 5-FU or 5-FU plus ubenimex, 3 also exhibited a superior antitumor efficiency even in our 5-FU-resistant mice model. Other antitumor agents could be conjugated with ubenimex using this strategy to obtain novel mutual prodrugs with promising antitumor potency. PMID:27322756

  13. 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.

  14. 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

  15. Tomato Fruits Show Wide Phenomic Diversity but Fruit Developmental Genes Show Low Genomic Diversity

    PubMed Central

    Mohan, Vijee; Gupta, Soni; Thomas, Sherinmol; Mickey, Hanjabam; Charakana, Chaitanya; Chauhan, Vineeta Singh; Sharma, Kapil; Kumar, Rakesh; Tyagi, Kamal; Sarma, Supriya; Gupta, Suresh Kumar; Kilambi, Himabindu Vasuki; Nongmaithem, Sapana; Kumari, Alka; Gupta, Prateek; Sreelakshmi, Yellamaraju; Sharma, Rameshwar

    2016-01-01

    Domestication of tomato has resulted in large diversity in fruit phenotypes. An intensive phenotyping of 127 tomato accessions from 20 countries revealed extensive morphological diversity in fruit traits. The diversity in fruit traits clustered the accessions into nine classes and identified certain promising lines having desirable traits pertaining to total soluble salts (TSS), carotenoids, ripening index, weight and shape. Factor analysis of the morphometric data from Tomato Analyzer showed that the fruit shape is a complex trait shared by several factors. The 100% variance between round and flat fruit shapes was explained by one discriminant function having a canonical correlation of 0.874 by stepwise discriminant analysis. A set of 10 genes (ACS2, COP1, CYC-B, RIN, MSH2, NAC-NOR, PHOT1, PHYA, PHYB and PSY1) involved in various plant developmental processes were screened for SNP polymorphism by EcoTILLING. The genetic diversity in these genes revealed a total of 36 non-synonymous and 18 synonymous changes leading to the identification of 28 haplotypes. The average frequency of polymorphism across the genes was 0.038/Kb. Significant negative Tajima’D statistic in two of the genes, ACS2 and PHOT1 indicated the presence of rare alleles in low frequency. Our study indicates that while there is low polymorphic diversity in the genes regulating plant development, the population shows wider phenotype diversity. Nonetheless, morphological and genetic diversity of the present collection can be further exploited as potential resources in future. PMID:27077652

  16. Promising antimicrobial capability of thin film metallic glasses.

    PubMed

    Chu, Y Y; Lin, Y S; Chang, C M; Liu, J-K; Chen, C H; Huang, J C

    2014-03-01

    Thin film metallic glasses (TFMGs) are demonstrated to exhibit excellent surface flatness, high corrosion resistance and satisfactory hydrophobic properties. Moreover, the antimicrobial and biocompatibility abilities of TFMGs are examined and the results are compared with the behavior of pure Ag and 316L stainless steel. Three TFMGs, Al48Ag37Ti15, Zr54Ti35Si11, and Zr59Ti22Ag19, are prepared by sputtering to assess the antimicrobial performance against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, which are the most common nosocomial infection pathogens. Experimental results show that the antimicrobial effect of the Al- or Ag-containing AlAgTi and ZrTiAg TFMGs is similar to that of the pure Ag coating. The ZrTiSi TFMG with no Ag or Al shows poor antimicrobial capability. The physical properties of highly smooth surface and hydrophobic nature alone are not sufficient to result in promising antimicrobial ability. The chemical metal ion release still plays a major role, which should be born in mind in designing biomedical devices. PMID:24433907

  17. 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.

  18. 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 Central Registration Agent, Selling Agent and Fiscal Agent. 107.1620 Section 107.1620 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance...

  19. 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...

  20. Do Pedagogical Agents Make a Difference to Student Motivation and Learning?

    ERIC Educational Resources Information Center

    Heidig, Steffi; Clarebout, Geraldine

    2011-01-01

    Pedagogical agents, characters that guide through multimedia learning environments, recently gained increasing interest. A review was published by Clarebout, Elen, Johnson and Shaw in 2002 where a lot of promises were made, but research on the motivational and learning effects of pedagogical agents was scarce. More than 70 articles on pedagogical…