NATURAL EMISSIONS OF NON-NETHANE VOLATILE ORGANIC COMPOUNDS, CARBON MONOXIDE, AND OXIDES OF NITROGEN FROM NORTH AMERICA. (R825419)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

A NEW APPROACH FOR ESTIMATING VOLATILE ORGANIC COMPOUND EMISSIONS FROM SEWERS: METHODOLOGY AND ASSOCIATED ERRORS. (R823335)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

INTERACTION OF POLYAROMATIC HYDROCARBONS (PAH)-RELATED COMPOUNDS WITH THE ALPHA AND BETA ISOFORMS OF THE ESTROGEN RECEPTOR. (R826301)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

SEDIMENT-AIR EQUILIBRIUM PARTITIONING OF SEMI-VOLATILE HYDROPHOBIC ORGANIC COMPOUNDS. PART 1. METHOD DEVELOPMENT AND WATER VAPOR SORPTION ISOTHERM. (R825513C017)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

A FOURIER TRANSFORM INFRARED PHOTOACOUSTIC SPECTROSCOPY (FTIR-PAS) STUDY OF THE ADSORPTION OF ORGANOPHOSPHORUS COMPOUNDS ON HEAT-TREATED MAGNESIUM OXIDE. (R825549C015)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Monomers for thermosetting and toughening epoxy resins. [glycidyl amine derivatives, propargyl-containing amines, and mutagenic testing of aromatic diamines

NASA Technical Reports Server (NTRS)

Pratt, J. R.

1981-01-01

Eight glycidyl amines were prepared by alkylating the parent amine with epichlorohydrin to form chlorohydrin, followed by cyclization with aqueous NaOH. Three of these compounds contained propargyl groups with postcuring studies. A procedure for quantitatively estimating the epoxy content of these glycidyl amines was employed for purity determination. Two diamond carbonates and several model propargly compounds were prepared. The synthesis of three new diamines, two which contain propargyloxy groups, and another with a sec-butyl group is in progress. These materials are at the dinitro stage ready for the final hydrogenation step. Four aromatic diamines were synthesized for mutagenic testing purposes. One of these compounds rapidly decomposes on exposure to air.

Immune drug discovery from venoms.

PubMed

Jimenez, Rocio; Ikonomopoulou, Maria P; Lopez, J Alejandro; Miles, John J

2018-01-01

This review catalogues recent advances in knowledge on venoms as standalone therapeutic agents or as blueprints for drug design, with an emphasis on venom-derived compounds that affects the immune system. We discuss venoms and venom-derived compounds that affect total immune cell numbers, immune cell proliferation, immune cell migration, immune cell phenotype and cytokine secretion. Identifying novel compounds that 'tune' the system, up-regulating the immune response during infectious disease and cancer and down-regulating the immune response during autoimmunity, will greatly expand the tool kit of human immunotherapeutics. Targeting these pathways may also open therapeutic options that alleviate symptoms of envenomation. Finally, combining recent advances in venomics with progress in low cost, high-throughput screening platforms will no doubt yield hundreds of prototype immune modulating compounds in the coming years. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immunomodulation and Anti-Inflammatory Effects of Garlic Compounds

PubMed Central

Arreola, Rodrigo; Quintero-Fabián, Saray; López-Roa, Rocío Ivette; Flores-Gutiérrez, Enrique Octavio; Reyes-Grajeda, Juan Pablo; Carrera-Quintanar, Lucrecia; Ortuño-Sahagún, Daniel

2015-01-01

The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates for maintaining the homeostasis of the immune system. The complex biochemistry of garlic makes it possible for variations in processing to yield different preparations with differences in final composition and compound proportion. In this review, we assess the most recent experimental results, which indicate that garlic appears to enhance the functioning of the immune system by stimulating certain cell types, such as macrophages, lymphocytes, natural killer (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage activation. Finally, because immune dysfunction plays an important role in the development and progress of several diseases, we critically examined immunoregulation by garlic extracts and compounds isolated, which can contribute to the treatment and prevention of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded that A. sativum modulates cytokine secretion and that such modulation may provide a mechanism of action for many of their therapeutic effects. PMID:25961060

Immunomodulation and anti-inflammatory effects of garlic compounds.

PubMed

Arreola, Rodrigo; Quintero-Fabián, Saray; López-Roa, Rocío Ivette; Flores-Gutiérrez, Enrique Octavio; Reyes-Grajeda, Juan Pablo; Carrera-Quintanar, Lucrecia; Ortuño-Sahagún, Daniel

2015-01-01

The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates for maintaining the homeostasis of the immune system. The complex biochemistry of garlic makes it possible for variations in processing to yield different preparations with differences in final composition and compound proportion. In this review, we assess the most recent experimental results, which indicate that garlic appears to enhance the functioning of the immune system by stimulating certain cell types, such as macrophages, lymphocytes, natural killer (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage activation. Finally, because immune dysfunction plays an important role in the development and progress of several diseases, we critically examined immunoregulation by garlic extracts and compounds isolated, which can contribute to the treatment and prevention of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded that A. sativum modulates cytokine secretion and that such modulation may provide a mechanism of action for many of their therapeutic effects.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis

PubMed Central

Patten, Shunmoogum A.; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary A.B.; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J. Alexander

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease. PMID:29202456

[Synthesis and regulation of flavor compounds derived from brewing yeast: Esters].

PubMed

Loviso, Claudia L; Libkind, Diego

2018-04-04

During brewing process yeast produce more than 500 chemical compounds that can negatively and positively impact beer at the organoleptic level. In recent years, and particularly thanks to the advancement of molecular biology and genomics, there has been considerable progress in our understanding about the molecular and cellular basis of the synthesis and regulation of many of these flavor compounds. This article focuses on esters, responsible for the floral and fruity beer flavor. Its formation depends on various enzymes and factors such as the concentration of wort nutrients, the amount of dissolved oxygen and carbon dioxide, fermentation temperature and mainly the genetics of the yeast used. We provide information about how the esters originate and how is the impact of different fermentative parameters on the final concentrations of these compounds and the quality of the end product. Copyright © 2018 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

PubMed

Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

2017-11-16

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

Recent Progress in Graphite Intercalation Compounds for Rechargeable Metal (Li, Na, K, Al)-Ion Batteries.

PubMed

Xu, Jiantie; Dou, Yuhai; Wei, Zengxi; Ma, Jianmin; Deng, Yonghong; Li, Yutao; Liu, Huakun; Dou, Shixue

2017-10-01

Lithium-ion batteries (LIBs) with higher energy density are very necessary to meet the increasing demand for devices with better performance. With the commercial success of lithiated graphite, other graphite intercalation compounds (GICs) have also been intensively reported, not only for LIBs, but also for other metal (Na, K, Al) ion batteries. In this Progress Report, we briefly review the application of GICs as anodes and cathodes in metal (Li, Na, K, Al) ion batteries. After a brief introduction on the development history of GICs, the electrochemistry of cationic GICs and anionic GICs is summarized. We further briefly summarize the use of cationic GICs and anionic GICs in alkali ion batteries and the use of anionic GICs in aluminium-ion batteries. Finally, we reach some conclusions on the drawbacks, major progress, emerging challenges, and some perspectives on the development of GICs for metal (Li, Na, K, Al) ion batteries. Further development of GICs for metal (Li, Na, K, Al) ion batteries is not only a strong supplement to the commercialized success of lithiated-graphite for LIBs, but also an effective strategy to develop diverse high-energy batteries for stationary energy storage in the future.

Recent Progress in Graphite Intercalation Compounds for Rechargeable Metal (Li, Na, K, Al)‐Ion Batteries

PubMed Central

Xu, Jiantie; Dou, Yuhai; Wei, Zengxi; Li, Yutao; Liu, Huakun; Dou, Shixue

2017-01-01

Abstract Lithium‐ion batteries (LIBs) with higher energy density are very necessary to meet the increasing demand for devices with better performance. With the commercial success of lithiated graphite, other graphite intercalation compounds (GICs) have also been intensively reported, not only for LIBs, but also for other metal (Na, K, Al) ion batteries. In this Progress Report, we briefly review the application of GICs as anodes and cathodes in metal (Li, Na, K, Al) ion batteries. After a brief introduction on the development history of GICs, the electrochemistry of cationic GICs and anionic GICs is summarized. We further briefly summarize the use of cationic GICs and anionic GICs in alkali ion batteries and the use of anionic GICs in aluminium‐ion batteries. Finally, we reach some conclusions on the drawbacks, major progress, emerging challenges, and some perspectives on the development of GICs for metal (Li, Na, K, Al) ion batteries. Further development of GICs for metal (Li, Na, K, Al) ion batteries is not only a strong supplement to the commercialized success of lithiated‐graphite for LIBs, but also an effective strategy to develop diverse high‐energy batteries for stationary energy storage in the future. PMID:29051856

Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease.

PubMed

Venigalla, Madhuri; Sonego, Sandra; Gyengesi, Erika; Sharman, Matthew J; Münch, Gerald

2016-05-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by deposition of amyloid plaques and neurofibrillary tangles, as well as microglial and astroglial activation, and, finally, leading to neuronal dysfunction and death. Current treatments for AD primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for the treatment of AD patients. This review will provide an overview of the antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of a variety of nutraceuticals including curcumin, apigenin, docosahexaenoic acid, epigallocatechin gallate, α-lipoic acid and resveratrol and their potential for AD prevention and treatment. We suggest that therapeutic use of these compounds might lead to a safe strategy to delay the onset of AD or slow down its progression. The continuing investigation of the potential of these substances is necessary as they are promising compounds to yield a possible remedy for this pervasive disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Conserved mechanisms of tumorigenesis in the Drosophila adult midgut.

PubMed

Martorell, Òscar; Merlos-Suárez, Anna; Campbell, Kyra; Barriga, Francisco M; Christov, Christo P; Miguel-Aliaga, Irene; Batlle, Eduard; Casanova, Jordi; Casali, Andreu

2014-01-01

Whereas the series of genetic events leading to colorectal cancer (CRC) have been well established, the precise functions that these alterations play in tumor progression and how they disrupt intestinal homeostasis remain poorly characterized. Activation of the Wnt/Wg signaling pathway by a mutation in the gene APC is the most common trigger for CRC, inducing benign lesions that progress to carcinomas due to the accumulation of other genetic alterations. Among those, Ras mutations drive tumour progression in CRC, as well as in most epithelial cancers. As mammalian and Drosophila's intestines share many similarities, we decided to explore the alterations induced in the Drosophila midgut by the combined activation of the Wnt signaling pathway with gain of function of Ras signaling in the intestinal stem cells. Here we show that compound Apc-Ras clones, but not clones bearing the individual mutations, expand as aggressive intestinal tumor-like outgrowths. These lesions reproduce many of the human CRC hallmarks such as increased proliferation, blockade of cell differentiation and cell polarity and disrupted organ architecture. This process is followed by expression of tumoral markers present in human lesions. Finally, a metabolic behavioral assay shows that these flies suffer a progressive deterioration in intestinal homeostasis, providing a simple readout that could be used in screens for tumor modifiers or therapeutic compounds. Taken together, our results illustrate the conservation of the mechanisms of CRC tumorigenesis in Drosophila, providing an excellent model system to unravel the events that, upon mutation in Apc and Ras, lead to CRC initiation and progression.

Recent advances in the research of inorganic nanotubes and fullerene-like nanoparticles

NASA Astrophysics Data System (ADS)

Tenne, Reshef

2014-06-01

This minireview outlines the main scientific directions in the research of inorganic nanotubes (INT) and fullerene-like (IF) nanoparticles from layered compounds, in recent years. In particular, this review describes to some detail the progress in the synthesis of new nanotubes, including those from misfit compounds; core-shell and the successful efforts to scale-up the synthesis of WS2 multiwall nanotubes. The high-temperature catalytic growth of nanotubes, via solar ablation is discussed as well. Furthermore, the doping of the IF-MoS2 nanoparticles and its influence on the physiochemical properties of the nanoparticles, including their interesting tribological properties are briefly discussed. Finally, the numerous applications of these nanoparticles as superior solid lubricants and for reinforcing variety of polymers are discussed in brief.

Development of Mushroom-Based Cosmeceutical Formulations with Anti-Inflammatory, Anti-Tyrosinase, Antioxidant, and Antibacterial Properties.

PubMed

Taofiq, Oludemi; Heleno, Sandrina A; Calhelha, Ricardo C; Alves, Maria José; Barros, Lillian; Barreiro, Maria Filomena; González-Paramás, Ana M; Ferreira, Isabel C F R

2016-10-14

The cosmetic industry is in a constant search for natural compounds or extracts with relevant bioactive properties, which became valuable ingredients to design cosmeceutical formulations. Mushrooms have been markedly studied in terms of nutritional value and medicinal properties. However, there is still slow progress in the biotechnological application of mushroom extracts in cosmetic formulations, either as antioxidants, anti-aging, antimicrobial, and anti-inflammatory agents or as hyperpigmentation correctors. In the present work, the cosmeceutical potential of ethanolic extracts prepared from Agaricus bisporus , Pleurotus ostreatus , and Lentinula edodes was analyzed in terms of anti-inflammatory, anti-tyrosinase, antioxidant, and antibacterial activities. The extracts were characterized in terms of phenolic acids and ergosterol composition, and further incorporated in a base cosmetic cream to achieve the same bioactive purposes. From the results obtained, the final cosmeceutical formulations presented 85%-100% of the phenolic acids and ergosterol levels found in the mushroom extracts, suggesting that there was no significant loss of bioactive compounds. The final cosmeceutical formulation also displayed all the ascribed bioactivities and as such, mushrooms can further be exploited as natural cosmeceutical ingredients.

A review of plant-based compounds and medicinal plants effective on atherosclerosis

PubMed Central

Sedighi, Mehrnoosh; Bahmani, Mahmoud; Asgary, Sedigheh; Beyranvand, Fatemeh; Rafieian-Kopaei, Mahmoud

2017-01-01

Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications. PMID:28461816

A review of plant-based compounds and medicinal plants effective on atherosclerosis.

PubMed

Sedighi, Mehrnoosh; Bahmani, Mahmoud; Asgary, Sedigheh; Beyranvand, Fatemeh; Rafieian-Kopaei, Mahmoud

2017-01-01

Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications.

Statistical molecular design of balanced compound libraries for QSAR modeling.

PubMed

Linusson, A; Elofsson, M; Andersson, I E; Dahlgren, M K

2010-01-01

A fundamental step in preclinical drug development is the computation of quantitative structure-activity relationship (QSAR) models, i.e. models that link chemical features of compounds with activities towards a target macromolecule associated with the initiation or progression of a disease. QSAR models are computed by combining information on the physicochemical and structural features of a library of congeneric compounds, typically assembled from two or more building blocks, and biological data from one or more in vitro assays. Since the models provide information on features affecting the compounds' biological activity they can be used as guides for further optimization. However, in order for a QSAR model to be relevant to the targeted disease, and drug development in general, the compound library used must contain molecules with balanced variation of the features spanning the chemical space believed to be important for interaction with the biological target. In addition, the assays used must be robust and deliver high quality data that are directly related to the function of the biological target and the associated disease state. In this review, we discuss and exemplify the concept of statistical molecular design (SMD) in the selection of building blocks and final synthetic targets (i.e. compounds to synthesize) to generate information-rich, balanced libraries for biological testing and computation of QSAR models.

One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke

PubMed Central

Chen, Han-Sen; Qi, Su-Hua; Shen, Jian-Gang

2017-01-01

Abstract: Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multi-target strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and blood-brain-barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds' studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy. PMID:27334020

Synthesis, Biological Evaluation, and Structure–Activity Relationships of Novel Substituted N-Phenyl Ureidobenzenesulfonate Derivatives Blocking Cell Cycle Progression in S-Phase and Inducing DNA Double-Strand Breaks

PubMed Central

2012-01-01

Twenty-eight new substituted N-phenyl ureidobenzenesulfonate (PUB-SO) and 18 N-phenylureidobenzenesulfonamide (PUB-SA) derivatives were prepared. Several PUB-SOs exhibited antiproliferative activity at the micromolar level against the HT-29, M21, and MCF-7 cell lines and blocked cell cycle progression in S-phase similarly to cisplatin. In addition, PUB-SOs induced histone H2AX (γH2AX) phosphorylation, indicating that these molecules induce DNA double-strand breaks. In contrast, PUB-SAs were less active than PUB-SOs and did not block cell cycle progression in S-phase. Finally, PUB-SOs 4 and 46 exhibited potent antitumor activity in HT-1080 fibrosarcoma cells grafted onto chick chorioallantoic membranes, which was similar to cisplatin and combretastatin A-4 and without significant toxicity toward chick embryos. These new compounds are members of a promising new class of anticancer agents. PMID:22694057

Synthesis, biological evaluation, and structure-activity relationships of novel substituted N-phenyl ureidobenzenesulfonate derivatives blocking cell cycle progression in S-phase and inducing DNA double-strand breaks.

PubMed

Turcotte, Vanessa; Fortin, Sébastien; Vevey, Florence; Coulombe, Yan; Lacroix, Jacques; Côté, Marie-France; Masson, Jean-Yves; C-Gaudreault, René

2012-07-12

Twenty-eight new substituted N-phenyl ureidobenzenesulfonate (PUB-SO) and 18 N-phenylureidobenzenesulfonamide (PUB-SA) derivatives were prepared. Several PUB-SOs exhibited antiproliferative activity at the micromolar level against the HT-29, M21, and MCF-7 cell lines and blocked cell cycle progression in S-phase similarly to cisplatin. In addition, PUB-SOs induced histone H2AX (γH2AX) phosphorylation, indicating that these molecules induce DNA double-strand breaks. In contrast, PUB-SAs were less active than PUB-SOs and did not block cell cycle progression in S-phase. Finally, PUB-SOs 4 and 46 exhibited potent antitumor activity in HT-1080 fibrosarcoma cells grafted onto chick chorioallantoic membranes, which was similar to cisplatin and combretastatin A-4 and without significant toxicity toward chick embryos. These new compounds are members of a promising new class of anticancer agents.

Profiling Animal Toxicants by Automatically Mining Public Bioassay Data: A Big Data Approach for Computational Toxicology

PubMed Central

Zhang, Jun; Hsieh, Jui-Hua; Zhu, Hao

2014-01-01

In vitro bioassays have been developed and are currently being evaluated as potential alternatives to traditional animal toxicity models. Already, the progress of high throughput screening techniques has resulted in an enormous amount of publicly available bioassay data having been generated for a large collection of compounds. When a compound is tested using a collection of various bioassays, all the testing results can be considered as providing a unique bio-profile for this compound, which records the responses induced when the compound interacts with different cellular systems or biological targets. Profiling compounds of environmental or pharmaceutical interest using useful toxicity bioassay data is a promising method to study complex animal toxicity. In this study, we developed an automatic virtual profiling tool to evaluate potential animal toxicants. First, we automatically acquired all PubChem bioassay data for a set of 4,841 compounds with publicly available rat acute toxicity results. Next, we developed a scoring system to evaluate the relevance between these extracted bioassays and animal acute toxicity. Finally, the top ranked bioassays were selected to profile the compounds of interest. The resulting response profiles proved to be useful to prioritize untested compounds for their animal toxicity potentials and form a potential in vitro toxicity testing panel. The protocol developed in this study could be combined with structure-activity approaches and used to explore additional publicly available bioassay datasets for modeling a broader range of animal toxicities. PMID:24950175

Profiling animal toxicants by automatically mining public bioassay data: a big data approach for computational toxicology.

PubMed

Zhang, Jun; Hsieh, Jui-Hua; Zhu, Hao

2014-01-01

In vitro bioassays have been developed and are currently being evaluated as potential alternatives to traditional animal toxicity models. Already, the progress of high throughput screening techniques has resulted in an enormous amount of publicly available bioassay data having been generated for a large collection of compounds. When a compound is tested using a collection of various bioassays, all the testing results can be considered as providing a unique bio-profile for this compound, which records the responses induced when the compound interacts with different cellular systems or biological targets. Profiling compounds of environmental or pharmaceutical interest using useful toxicity bioassay data is a promising method to study complex animal toxicity. In this study, we developed an automatic virtual profiling tool to evaluate potential animal toxicants. First, we automatically acquired all PubChem bioassay data for a set of 4,841 compounds with publicly available rat acute toxicity results. Next, we developed a scoring system to evaluate the relevance between these extracted bioassays and animal acute toxicity. Finally, the top ranked bioassays were selected to profile the compounds of interest. The resulting response profiles proved to be useful to prioritize untested compounds for their animal toxicity potentials and form a potential in vitro toxicity testing panel. The protocol developed in this study could be combined with structure-activity approaches and used to explore additional publicly available bioassay datasets for modeling a broader range of animal toxicities.

Acrylamide in coffee: review of progress in analysis, formation and level reduction.

PubMed

Guenther, Helmut; Anklam, Elke; Wenzl, Thomas; Stadler, Richard H

2007-01-01

This paper summarizes the progress made in understanding the formation of acrylamide in coffee, as well as potential reduction strategies, as presented during the joint CIAA/EC workshop on acrylamide, held in Brussels in March 2006. Currently, there are no concrete measures to reduce acrylamide concentrations in roast and ground coffee without appreciably changing the organoleptic properties of the product. Certain approaches, such as steam roasting, have been tried on a laboratory scale, albeit without affording a significant reduction. More work on the mechanisms governing the "loss" of acrylamide during storage of roast and ground coffee is warranted, and studies in this direction have been initiated. Finally, risk/benefit analysis must be addressed in a complex food such as coffee, known to harbour numerous health beneficial/chemoprotective compounds with antioxidant and antimutagenic properties.

Molecular insights of protein contour recognition with ligand pharmacophoric sites through combinatorial library design and MD simulation in validating HTLV-1 PR inhibitors.

PubMed

Selvaraj, Chandrabose; Omer, Ankur; Singh, Poonam; Singh, Sanjeev Kumar

2015-01-01

Retroviruses HIV-1 and HTLV-1 are chiefly considered to be the most dangerous pathogens in Homo sapiens. These two viruses have structurally unique protease (PR) enzymes, which are having common function of its replication mechanism. Though HIV PR drugs failed to inhibit HTLV-1 infections, they emphatically emphasise the need for designing new lead compounds against HTLV-1 PR. Therefore, we tried to understand the binding level interactions through the charge environment present in both ligand and protein active sites. The domino effect illustrates that libraries of purvalanol-A are attuned to fill allosteric binding site of HTLV-1 PR through molecular recognition and shows proper binding of ligand pharmacophoric features in receptor contours. Our screening evaluates seven compounds from purvalanol-A libraries, and these compounds' pharmacophore searches for an appropriate place in the binding site and it places well according to respective receptor contour surfaces. Thus our result provides a platform for the progress of more effective compounds, which are better in free energy calculation, molecular docking, ADME and molecular dynamics studies. Finally, this research provided novel chemical scaffolds for HTLV-1 drug discovery.

Insecticide resistance resulting from sequential selection of houseflies in the field by organophosphorus compounds*

PubMed Central

Georghiou, George P.; Hawley, Marilyn K.

1971-01-01

Although cross-resistance in houseflies to the organophosphates has eliminated numerous potentially useful compounds from field use, the ”subgroup” specificity of this phenomenon has permitted housefly control to be carried out for nearly a quarter of a century by changing from one toxicant to another within this class of insecticides. A question of considerable importance in insect control is whether the development of resistance to one subgroup of organophosphates will be at the expense of resistance to a subgroup applied previously. The development over several years of resistance in a field population selected sequentially by a number of organophosphates was studied. It was observed that the resistance spectrum expanded progressively to include, finally, organophosphates originally thought to belong to more than one subgroup—namely, malathion (resistance greater than 100 times), fenchlorphos (114 times), diazinon (163 times), coumaphos (greater than 100 times), Ciodrin (greater than 100 times), fenthion (18 times) and naled (9.3 times). Resistance to each compound continued to rise to levels considerably higher than those achieved at the time when the field use of the compound ended. The possible coexistence of subgroup cross-resistance in a population is discussed in the light of these results. PMID:5316852

Plastids of Marine Phytoplankton Produce Bioactive Pigments and Lipids

PubMed Central

Heydarizadeh, Parisa; Poirier, Isabelle; Loizeau, Damien; Ulmann, Lionel; Mimouni, Virginie; Schoefs, Benoît; Bertrand, Martine

2013-01-01

Phytoplankton is acknowledged to be a very diverse source of bioactive molecules. These compounds play physiological roles that allow cells to deal with changes of the environmental constrains. For example, the diversity of light harvesting pigments allows efficient photosynthesis at different depths in the seawater column. Identically, lipid composition of cell membranes can vary according to environmental factors. This, together with the heterogenous evolutionary origin of taxa, makes the chemical diversity of phytoplankton compounds much larger than in terrestrial plants. This contribution is dedicated to pigments and lipids synthesized within or from plastids/photosynthetic membranes. It starts with a short review of cyanobacteria and microalgae phylogeny. Then the bioactivity of pigments and lipids (anti-oxidant, anti-inflammatory, anti-mutagenic, anti-cancer, anti-obesity, anti-allergic activities, and cardio- neuro-, hepato- and photoprotective effects), alone or in combination, is detailed. To increase the cellular production of bioactive compounds, specific culture conditions may be applied (e.g., high light intensity, nitrogen starvation). Regardless of the progress made in blue biotechnologies, the production of bioactive compounds is still limited. However, some examples of large scale production are given, and perspectives are suggested in the final section. PMID:24022731

Technology Roadmaps for Compound Semiconductors

PubMed Central

Bennett, Herbert S.

2000-01-01

The roles cited for compound semiconductors in public versions of existing technology roadmaps from the National Electronics Manufacturing Initiative, Inc., Optoelectronics Industry Development Association, Microelectronics Advanced Research Initiative on Optoelectronic Interconnects, and Optoelectronics Industry and Technology Development Association (OITDA) are discussed and compared within the context of trends in the Si CMOS industry. In particular, the extent to which these technology roadmaps treat compound semiconductors at the materials processing and device levels will be presented for specific applications. For example, OITDA’s Optical Communications Technology Roadmap directly connects the information demand of delivering 100 Mbit/s to the home to the requirement of producing 200 GHz heterojunction bipolar transistors with 30 nm bases and InP high electron mobility transistors with 100 nm gates. Some general actions for progress towards the proposed International Technology Roadmap for Compound Semiconductors (ITRCS) and methods for determining the value of an ITRCS will be suggested. But, in the final analysis, the value added by an ITRCS will depend on how industry leaders respond. The technical challenges and economic opportunities of delivering high quality digital video to consumers provide concrete examples of where the above actions and methods could be applied. PMID:27551615

Chinese Herbal Medicine Meets Biological Networks of Complex Diseases: A Computational Perspective

PubMed Central

Gu, Shuo

2017-01-01

With the rapid development of cheminformatics, computational biology, and systems biology, great progress has been made recently in the computational research of Chinese herbal medicine with in-depth understanding towards pharmacognosy. This paper summarized these studies in the aspects of computational methods, traditional Chinese medicine (TCM) compound databases, and TCM network pharmacology. Furthermore, we chose arachidonic acid metabolic network as a case study to demonstrate the regulatory function of herbal medicine in the treatment of inflammation at network level. Finally, a computational workflow for the network-based TCM study, derived from our previous successful applications, was proposed. PMID:28690664

Chinese Herbal Medicine Meets Biological Networks of Complex Diseases: A Computational Perspective.

PubMed

Gu, Shuo; Pei, Jianfeng

2017-01-01

With the rapid development of cheminformatics, computational biology, and systems biology, great progress has been made recently in the computational research of Chinese herbal medicine with in-depth understanding towards pharmacognosy. This paper summarized these studies in the aspects of computational methods, traditional Chinese medicine (TCM) compound databases, and TCM network pharmacology. Furthermore, we chose arachidonic acid metabolic network as a case study to demonstrate the regulatory function of herbal medicine in the treatment of inflammation at network level. Finally, a computational workflow for the network-based TCM study, derived from our previous successful applications, was proposed.

ET Toxic Metals Replacement Review SEA Spring Face to Face

NASA Technical Reports Server (NTRS)

Pratz, Earl

2007-01-01

The information contained in the presentation covers development work carried out under SDS projects. The intent of the effort is to find chrome(VI) free alternates to our current chromated processing solutions. The information presented reports progress in work aimed to replace our alkaline cleaner (Turco 4215), conversion coat (Iridite 14-2) and chrome (VI) compounds used in LOx tank hydrostatic proof test solution. To date we have found candidates for use in the proof test solution and alkaline cleaner. These candidates are in the final stages of testing. Lab data is reported in the presentation.

Dearomative dihydroxylation with arenophiles

NASA Astrophysics Data System (ADS)

Southgate, Emma H.; Pospech, Jola; Fu, Junkai; Holycross, Daniel R.; Sarlah, David

2016-10-01

Aromatic hydrocarbons are some of the most elementary feedstock chemicals, produced annually on a million metric ton scale, and are used in the production of polymers, paints, agrochemicals and pharmaceuticals. Dearomatization reactions convert simple, readily available arenes into more complex molecules with broader potential utility, however, despite substantial progress and achievements in this field, there are relatively few methods for the dearomatization of simple arenes that also selectively introduce functionality. Here we describe a new dearomatization process that involves visible-light activation of small heteroatom-containing organic molecules—arenophiles—that results in their para-cycloaddition with a variety of aromatic compounds. The approach uses N-N-arenophiles to enable dearomative dihydroxylation and diaminodihydroxylation of simple arenes. This strategy provides direct and selective access to highly functionalized cyclohexenes and cyclohexadienes and is orthogonal to existing chemical and biological dearomatization processes. Finally, we demonstrate the synthetic utility of this strategy with the concise synthesis of several biologically active compounds and natural products.

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

Marine derived xyloketal derivatives exhibit anti-stress and anti-ageing effects through HSF pathway in Caenorhabditis elegans.

PubMed

Zhou, Jie-Bin; Zheng, Ying-Lin; Zeng, Yi-Xuan; Wang, Jia-Wei; Pei, Zhong; Pang, Ji-Yan

2018-03-25

Ageing is a complex but universal phenomenon that progressively challenges the homeostasis network and finally leads to the dysfunction of organisms and even death. Previous studies demonstrated that xyloketal B and its derivatives, a series of marine novel ketone compounds, possessed unique antioxidative effects on endothelial and neuronal oxidative injuries. In this study, we examined the effects of xyloketal derivatives on extending lifespan and healthspan of Caenorhabditis elegans. The results showed that most selected xyloketals could protect Caenorhabditis elegans against heat stress and extend the lifespan of worms. Compound 15, a benzo-1, 3-oxazine xyloketal derivative, possessed most potent effect in anti-heat stress assay and significantly attenuated ageing-related decrease of pumping and bending of the worms in healthspan assay. In addition, the beneficial effect of 15 was abolished in PS3551 worms, a strain that possesses non-functional heat shock transcription factor-1 (HSF-1). Furthermore, 15 increased the expression of heat shock protein 70 (HSP70), a downstream molecular chaperone of HSF-1. These results indicated that HSF-1 might contribute to the protective effect of this compound in Caenorhabditis elegans ageing. Molecular docking studies suggested that these xyloketal derivatives were bound to the DNA binding domain of HSF-1, promoted the conformation of HSF-1, thus strengthened the interaction between the HSF-1 and related DNA. ALA-67, ASN-74 and LYS-80 of binding region might be the key amino residues during the interaction. Finally, compound 15 could reduce the paralysis of the CL4176 worms, a transgenic strain expressing human Aβ 3-42 under a temperature-inducible system. Collectively, these data indicate that xyloketals have potential implications for further evaluation in anti-ageing studies. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

[Pharmacotherapy of Parkinson's disease: progress or regress?].

PubMed

Pytka, Karolina; Zygmunt, Małgorzata; Filipek, Barbara

2013-07-24

Parkinson's disease (PD) is a chronic, progressive disease of the central nervous system (CNS), characterized by a slow loss of dopaminergic neurons in the substantia nigra, leading to significant decrease in dopamine (DA) levels in the striatum. Currently used drugs, such as levodopa (L-DOPA), amantadine, dopamine agonists (D) or anticholinergic drugs, are not effective enough, and do not eliminate the causes of disease. Many research centers are conducting research on new forms of currently used drugs (e.g. Duodopa, XP21279, IPX066), new drugs of already known groups (e.g. safinamide), medicines that suppress side effects of L-DOPA (e.g. AFQ056, fipamezole), and, finally, compounds with a novel mechanism of action (e.g. PMY50028, A2A receptor antagonists). A lot of scientific reports indicate an important role of A2A receptors in the regulation of the central movement system, so a new group of compounds - selective antagonists of A2A receptors (e.g. istradefylline, preladenant, SYN115) - has been developed and their potential use in PD has been examined. Clinical studies of A2A receptor antagonists have shown that this group of compounds can shorten off periods and at the same time they do not worsen dyskinesias in patients with PD. Moreover, there is ongoing research on new forms of treatment, such as gene therapy. Attempts to apply the viral vector AAV-2, which will be able to infect neurons with a variety of genes, including the gene of glutamate decarboxylase (GAD), neurturin (NTN), or aromatic L-amino acid decarboxylase, are currently being carried out. The results of phase I and II clinical studies showed some efficacy of this form of treatment, but the method requires further studies. An analysis of potential future therapies of Parkinson's disease suggests that some progress in this field has been made.

A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells

PubMed Central

Peng, Jian-long; Wang, Shi-jie; Geng, Jie-jie; Liu, Ji-de; Feng, Fei; Song, Fei; Li, Ling; Zhu, Ping; Jiang, Jian-li; Chen, Zhi-nan

2016-01-01

CD147, a type I transmembrane glycoprotein, is highly expressed in various cancer types and plays important roles in tumor progression, especially by promoting the motility and invasion of hepatocellular carcinoma (HCC) cells. These crucial roles make CD147 an attractive target for therapeutic intervention in HCC, but no small-molecule inhibitors of CD147 have been developed to date. To identify a candidate inhibitor, we used a pharmacophore model derived from the structure of CD147 to virtually screen over 300,000 compounds. The 100 highest-ranked compounds were subjected to biological assays, and the most potent one, dubbed AC-73 (ID number: AN-465/42834501), was studied further. We confirmed that AC-73 targeted CD147 and further demonstrated it can specifically disrupt CD147 dimerization. Moreover, molecular docking and mutagenesis experiments showed that the possible binding sites of AC-73 on CD147 included Glu64 and Glu73 in the N-terminal IgC2 domain, which two residues are located in the dimer interface of CD147. Functional assays revealed that AC-73 inhibited the motility and invasion of typical HCC cells, but not HCC cells that lacked the CD147 gene, demonstrating on-target action. Further, AC-73 reduced HCC metastasis by suppressing matrix metalloproteinase (MMP)-2 via down-regulation of the CD147/ERK1/2/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, AC-73 attenuated progression in an orthotopic nude mouse model of liver metastasis, suggesting that AC-73 or its derivatives have potential for use in HCC intervention. We conclude that the novel small-molecule inhibitor AC-73 inhibits HCC mobility and invasion, probably by disrupting CD147 dimerization and thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways, which are crucial for cancer progression. PMID:26882566

A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells.

PubMed

Fu, Zhi-guang; Wang, Li; Cui, Hong-yong; Peng, Jian-long; Wang, Shi-jie; Geng, Jie-jie; Liu, Ji-de; Feng, Fei; Song, Fei; Li, Ling; Zhu, Ping; Jiang, Jian-li; Chen, Zhi-nan

2016-02-23

CD147, a type I transmembrane glycoprotein, is highly expressed in various cancer types and plays important roles in tumor progression, especially by promoting the motility and invasion of hepatocellular carcinoma (HCC) cells. These crucial roles make CD147 an attractive target for therapeutic intervention in HCC, but no small-molecule inhibitors of CD147 have been developed to date. To identify a candidate inhibitor, we used a pharmacophore model derived from the structure of CD147 to virtually screen over 300,000 compounds. The 100 highest-ranked compounds were subjected to biological assays, and the most potent one, dubbed AC-73 (ID number: AN-465/42834501), was studied further. We confirmed that AC-73 targeted CD147 and further demonstrated it can specifically disrupt CD147 dimerization. Moreover, molecular docking and mutagenesis experiments showed that the possible binding sites of AC-73 on CD147 included Glu64 and Glu73 in the N-terminal IgC2 domain, which two residues are located in the dimer interface of CD147. Functional assays revealed that AC-73 inhibited the motility and invasion of typical HCC cells, but not HCC cells that lacked the CD147 gene, demonstrating on-target action. Further, AC-73 reduced HCC metastasis by suppressing matrix metalloproteinase (MMP)-2 via down-regulation of the CD147/ERK1/2/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, AC-73 attenuated progression in an orthotopic nude mouse model of liver metastasis, suggesting that AC-73 or its derivatives have potential for use in HCC intervention. We conclude that the novel small-molecule inhibitor AC-73 inhibits HCC mobility and invasion, probably by disrupting CD147 dimerization and thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways, which are crucial for cancer progression.

Inhibition of HIV-1 by curcumin A, a novel curcumin analog

PubMed Central

Kumari, Namita; Kulkarni, Amol A; Lin, Xionghao; McLean, Charlee; Ammosova, Tatiana; Ivanov, Andrey; Hipolito, Maria; Nekhai, Sergei; Nwulia, Evaristus

2015-01-01

Despite the remarkable success of combination antiretroviral therapy at curtailing HIV progression, emergence of drug-resistant viruses, chronic low-grade inflammation, and adverse effects of combination antiretroviral therapy treatments, including metabolic disorders collectively present the impetus for development of newer and safer antiretroviral drugs. Curcumin, a phytochemical compound, was previously reported to have some in vitro anti-HIV and anti-inflammatory activities, but poor bioavailability has limited its clinical utility. To circumvent the bioavailability problem, we derivatized curcumin to sustain retro-aldol decomposition at physiological pH. The lead compound derived, curcumin A, showed increased stability, especially in murine serum where it was stable for up to 25 hours, as compared to curcumin that only had a half-life of 10 hours. Both curcumin and curcumin A showed similar inhibition of one round of HIV-1 infection in cultured lymphoblastoid (also called CEM) T cells (IC50=0.7 μM). But in primary peripheral blood mononuclear cells, curcumin A inhibited HIV-1 more potently (IC50=2 μM) compared to curcumin (IC50=12 μM). Analysis of specific steps of HIV-1 replication showed that curcumin A inhibited HIV-1 reverse transcription, but had no effect on HIV-1 long terminal repeat basal or Tat-induced transcription, or NF-κB-driven transcription at low concentrations that affected reverse transcription. Finally, we showed curcumin A induced expression of HO-1 and decreased cell cycle progression of T cells. Our findings thus indicate that altering the core structure of curcumin could yield more stable compounds with potent antiretroviral and anti-inflammatory activities. PMID:26366056

Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice

PubMed Central

Kuznetsova, Alexandra; Yu, Yue; Hollister-Lock, Jennifer; Opare-Addo, Lynn; Rozzo, Aldo; Sadagurski, Marianna; Norquay, Lisa; Reed, Jessica E.; El Khattabi, Ilham; Bonner-Weir, Susan; Weir, Gordon C.; Sharma, Arun

2016-01-01

The capacity of pancreatic β cells to maintain glucose homeostasis during chronic physiologic and immunologic stress is important for cellular and metabolic homeostasis. Insulin receptor substrate 2 (IRS2) is a regulated adapter protein that links the insulin and IGF1 receptors to downstream signaling cascades. Since strategies to maintain or increase IRS2 expression can promote β cell growth, function, and survival, we conducted a screen to find small molecules that can increase IRS2 mRNA in isolated human pancreatic islets. We identified 77 compounds, including 15 that contained a tricyclic core. To establish the efficacy of our approach, one of the tricyclic compounds, trimeprazine tartrate, was investigated in isolated human islets and in mouse models. Trimeprazine is a first-generation antihistamine that acts as a partial agonist against the histamine H1 receptor (H1R) and other GPCRs, some of which are expressed on human islets. Trimeprazine promoted CREB phosphorylation and increased the concentration of IRS2 in islets. IRS2 was required for trimeprazine to increase nuclear Pdx1, islet mass, β cell replication and function, and glucose tolerance in mice. Moreover, trimeprazine synergized with anti-CD3 Abs to reduce the progression of diabetes in NOD mice. Finally, it increased the function of human islet transplants in streptozotocin-induced (STZ-induced) diabetic mice. Thus, trimeprazine, its analogs, or possibly other compounds that increase IRS2 in islets and β cells without adverse systemic effects might provide mechanism-based strategies to prevent the progression of diabetes. PMID:27152363

Bioremediation and phytoremediation: Chlorinated and recalcitrant compounds

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

NONE

1998-12-31

Bioremediation and phytoremediation have progressed, especially with regard to the treatment of hydrocarbon-contaminated sites. Sites contaminated with chlorinated and recalcitrant compounds have proven more resistant to these approaches, but exciting progress is being made both in the laboratory and in the field. This book brings together the latest breakthrough thinking and results in bioremediation, with chapters on cometabolic processes, aerobic and anaerobic mechanisms, biological reductive dechlorination processes, bioaugmentation, biomonitoring, and phytoremediation of recalcitrant organic compounds.

Monitoring of Yeast Communities and Volatile Flavor Changes During Traditional Korean Soy Sauce Fermentation.

PubMed

Song, Young-Ran; Jeong, Do-Youn; Baik, Sang-Ho

2015-09-01

Flavor development in soy sauce is significantly related to the diversity of yeast species. Due to its unique fermentation with meju, the process of making Korean soy sauce gives rise to a specific yeast community and, therefore, flavor profile; however, no detailed analysis of the identifying these structure has been performed. Changes in yeast community structure during Korean soy sauce fermentation were examined using both culture-dependent and culture-independent methods with simultaneous analysis of the changes in volatile compounds by GC-MS analysis. During fermentation, Candida, Pichia, and Rhodotorula sp. were the dominant species, whereas Debaryomyces, Torulaspora, and Zygosaccharomyces sp. were detected only at the early stage. In addition, Cryptococcus, Microbotryum, Tetrapisispora, and Wickerhamomyces were detected as minor strains. Among the 62 compounds identified in this study, alcohols, ketones, and pyrazines were present as the major groups during the initial stages, whereas the abundance of acids with aldehydes increased as the fermentation progressed. Finally, the impacts of 10 different yeast strains found to participate in fermentation on the formation of volatile compounds were evaluated under soy-based conditions. It was revealed that specific species produced different profiles of volatile compounds, some of which were significant flavor contributors, especially volatile alcohols, aldehydes, esters, and ketones. © 2015 Institute of Food Technologists®

Inter-laboratory assessment of a harmonized zebrafish developmental toxicology assay - progress report on phase I.

PubMed

Gustafson, A-L; Stedman, D B; Ball, J; Hillegass, J M; Flood, A; Zhang, C X; Panzica-Kelly, J; Cao, J; Coburn, A; Enright, B P; Tornesi, M B; Hetheridge, M; Augustine-Rauch, K A

2012-04-01

This report provides a progress update of a consortium effort to develop a harmonized zebrafish developmental toxicity assay. Twenty non-proprietary compounds (10 animal teratogens and 10 animal non-teratogens) were evaluated blinded in 4 laboratories. Zebrafish embryos from pond-derived and cultivated strain wild types were exposed to the test compounds for 5 days and subsequently evaluated for lethality and morphological changes. Each of the testing laboratories achieved similar overall concordance to the animal data (60-70%). Subsequent optimization procedures to improve the overall concordance focused on compound formulation and test concentration adjustments, chorion permeation and number of replicates. These optimized procedures were integrated into a revised protocol and all compounds were retested in one lab using embryos from pond-derived zebrafish and achieved 85% total concordance. To further assess assay performance, a study of additional compounds is currently in progress at two laboratories using embryos from pond-derived and cultivated-strain wild type zebrafish. Copyright © 2011 Elsevier Inc. All rights reserved.

Biodegradation of Aromatic Compounds by Escherichia coli

PubMed Central

Díaz, Eduardo; Ferrández, Abel; Prieto, María A.; García, José L.

2001-01-01

Although Escherichia coli has long been recognized as the best-understood living organism, little was known about its abilities to use aromatic compounds as sole carbon and energy sources. This review gives an extensive overview of the current knowledge of the catabolism of aromatic compounds by E. coli. After giving a general overview of the aromatic compounds that E. coli strains encounter and mineralize in the different habitats that they colonize, we provide an up-to-date status report on the genes and proteins involved in the catabolism of such compounds, namely, several aromatic acids (phenylacetic acid, 3- and 4-hydroxyphenylacetic acid, phenylpropionic acid, 3-hydroxyphenylpropionic acid, and 3-hydroxycinnamic acid) and amines (phenylethylamine, tyramine, and dopamine). Other enzymatic activities acting on aromatic compounds in E. coli are also reviewed and evaluated. The review also reflects the present impact of genomic research and how the analysis of the whole E. coli genome reveals novel aromatic catabolic functions. Moreover, evolutionary considerations derived from sequence comparisons between the aromatic catabolic clusters of E. coli and homologous clusters from an increasing number of bacteria are also discussed. The recent progress in the understanding of the fundamentals that govern the degradation of aromatic compounds in E. coli makes this bacterium a very useful model system to decipher biochemical, genetic, evolutionary, and ecological aspects of the catabolism of such compounds. In the last part of the review, we discuss strategies and concepts to metabolically engineer E. coli to suit specific needs for biodegradation and biotransformation of aromatics and we provide several examples based on selected studies. Finally, conclusions derived from this review may serve as a lead for future research and applications. PMID:11729263

Identifying natural compounds as multi-target-directed ligands against Alzheimer's disease: an in silico approach.

PubMed

Ambure, Pravin; Bhat, Jyotsna; Puzyn, Tomasz; Roy, Kunal

2018-04-23

Alzheimer's disease (AD) is a multi-factorial disease, which can be simply outlined as an irreversible and progressive neurodegenerative disorder with an unclear root cause. It is a major cause of dementia in old aged people. In the present study, utilizing the structural and biological activity information of ligands for five important and mostly studied vital targets (i.e. cyclin-dependant kinase 5, β-secretase, monoamine oxidase B, glycogen synthase kinase 3β, acetylcholinesterase) that are believed to be effective against AD, we have developed five classification models using linear discriminant analysis (LDA) technique. Considering the importance of data curation, we have given more attention towards the chemical and biological data curation, which is a difficult task especially in case of big data-sets. Thus, to ease the curation process we have designed Konstanz Information Miner (KNIME) workflows, which are made available at http://teqip.jdvu.ac.in/QSAR_Tools/ . The developed models were appropriately validated based on the predictions for experiment derived data from test sets, as well as true external set compounds including known multi-target compounds. The domain of applicability for each classification model was checked based on a confidence estimation approach. Further, these validated models were employed for screening of natural compounds collected from the InterBioScreen natural database ( https://www.ibscreen.com/natural-compounds ). Further, the natural compounds that were categorized as 'actives' in at least two classification models out of five developed models were considered as multi-target leads, and these compounds were further screened using the drug-like filter, molecular docking technique and then thoroughly analyzed using molecular dynamics studies. Finally, the most potential multi-target natural compounds against AD are suggested.

Presence of novel compound BCR-ABL mutations in late chronic and advanced phase imatinib sensitive CML patients indicates their possible role in CML progression.

PubMed

Akram, Afia Muhammad; Iqbal, Zafar; Akhtar, Tanveer; Khalid, Ahmed Mukhtar; Sabar, Muhammad Farooq; Qazi, Mahmood Hussain; Aziz, Zeba; Sajid, Nadia; Aleem, Aamer; Rasool, Mahmood; Asif, Muhammad; Aloraibi, Saleh; Aljamaan, Khaled; Iqbal, Mudassar

2017-04-03

BCR-ABL kinase domain (K D ) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients. Therefore, we investigated presence of ABL-K D mutations in chronic phase (n = 41), late chronic phase (n = 33) and accelerated phase (n = 16) imatinib responders. Direct sequencing analysis was used for this purpose. Eleven patients (12.22%) in late-CP CML were detected having total 24 types of point mutations, out of which 8 (72.72%) harbored compound mutated sites. SH2 contact site mutations were dominant in our study cohort, with E355G (3.33%) being the most prevalent. Five patients (45%) all having compound mutated sites, progressed to advanced phases of disease during follow up studies. Two novel silent mutations G208G and E292E/E were detected in combination with other mutants, indicating limited tolerance for BCR-ABL1 kinase domain for missense mutations. However, no patient in early CP of disease manifested mutated ABL-K D . Occurrence of mutations was found associated with elevated platelet count (p = 0.037) and patients of male sex (p = 0.049). The median overall survival and event free survival of CML patients (n = 90) was 6.98 and 5.8 y respectively. The compound missense mutations in BCR-ABL kinase domain responsible to elicit disease progression, drug resistance or disease relapse in CML, can be present in yet Imatinib sensitive patients. Disease progression observed here, emphasizes the need of ABL-K D mutation screening in late chronic phase CML patients for improved clinical management of disease.

31P NMR spectroscopy in the quality control and authentication of extra-virgin olive oil: a review of recent progress.

PubMed

Dais, Photis; Spyros, Apostolos

2007-05-01

This review is a brief account on the application of a novel methodology to the quality control and authentication of extra-virgin olive oil. This methodology is based on the derivatization of the labile hydrogens of functional groups, such as hydroxyl and carboxyl groups, of olive oil constituents with the phosphorus reagent 2-chloro-4,4,5,5-tetramethyldioxaphospholane, and the use of the (31)P chemical shifts to identify the phosphitylated compounds. Various experimental aspects such as pertinent instrumentation, sample preparation, acquisition parameters and properties of the phosphorus reagent are reviewed. The strategy to assign the (31)P signals of the phosphitylated model compounds and olive oil constituents by employing 1D and 2D NMR experiments is presented. Finally, the capability of this technique to assess the quality and the genuineness of extra-virgin olive oil and to detect fraud is discussed. Copyright (c) 2007 John Wiley & Sons, Ltd.

Chemical Space: Big Data Challenge for Molecular Diversity.

PubMed

Awale, Mahendra; Visini, Ricardo; Probst, Daniel; Arús-Pous, Josep; Reymond, Jean-Louis

2017-10-25

Chemical space describes all possible molecules as well as multi-dimensional conceptual spaces representing the structural diversity of these molecules. Part of this chemical space is available in public databases ranging from thousands to billions of compounds. Exploiting these databases for drug discovery represents a typical big data problem limited by computational power, data storage and data access capacity. Here we review recent developments of our laboratory, including progress in the chemical universe databases (GDB) and the fragment subset FDB-17, tools for ligand-based virtual screening by nearest neighbor searches, such as our multi-fingerprint browser for the ZINC database to select purchasable screening compounds, and their application to discover potent and selective inhibitors for calcium channel TRPV6 and Aurora A kinase, the polypharmacology browser (PPB) for predicting off-target effects, and finally interactive 3D-chemical space visualization using our online tools WebDrugCS and WebMolCS. All resources described in this paper are available for public use at www.gdb.unibe.ch.

Inorganic Nanotubes and Fullerene-like Nanoparticles at the Crossroads between Solid-State Chemistry and Nanotechnology.

PubMed

Višić, Bojana; Panchakarla, Leela Srinivas; Tenne, Reshef

2017-09-20

Inorganic nanotubes (NTs) and fullerene-like nanoparticles (NPs) of WS 2 were discovered some 25 years ago and are produced now on a commercial scale for various applications. This Perspective provides a brief description of recent progress in this scientific discipline. The conceptual evolution leading to the discovery of these NTs and NPs is briefly discussed. Subsequently, recent progress in the synthesis of such NPs from a variety of inorganic compounds with layered (2D) structure is described. In particular, we discuss the synthesis of NTs from chalcogenide- and oxide-based ternary misfit layered compounds, as well as their structure and different growth mechanisms. Next we deliberate on the mechanical, optical, electrical, and electromechanical properties, which delineate them from their bulk counterparts and also from their graphene-like analogues. Here, different experiments with individual NTs coupled with first-principles and molecular dynamics calculations demonstrate the unique physical nature of these quasi-1D nanostructures. Finally, the various applications of the fullerene-like NPs of WS 2 and NTs formed therefrom are deliberated. Foremost among the possibilities are their extensive uses as superior solid lubricants. Combined with their nontoxicity and their facile dispersion, these NTs, with an ultimate strength of about 20 GPa, are likely to find numerous applications in reinforcing polymers, adhesives, textiles, medical devices, metallic alloys, and even concrete. Other potential applications in energy-harvesting and catalysis are discussed in brief.

IRIS Toxicological Review of Thallium and Compounds (Final Report)

EPA Science Inventory

EPA has finalized the Toxicological Review of Thallium and Compounds: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

Novel inhibitors of the cellular renin-angiotensin system components, poricoic acids, target Smad3 phosphorylation and Wnt/β-catenin pathway against renal fibrosis.

PubMed

Wang, Ming; Chen, Dan-Qian; Chen, Lin; Cao, Gang; Zhao, Hui; Liu, Dan; Vaziri, Nosratola D; Guo, Yan; Zhao, Ying-Yong

2018-07-01

Tubulo-interstitial fibrosis is the final pathway in the progression of chronic kidney disease (CKD) to kidney failure. The renin-angiotensin system (RAS) plays a major role in CKD progression. Hence, we determined the efficacy of novel RAS inhibitors isolated from Poria cocos against renal fibrosis. Effects of three novel tetracyclic triterpenoid compounds, poricoic acid ZC (PZC), poricoic acid ZD (PZD) and poricoic acid ZE (PZE), were investigated on TGFβ1- and angiotensin II (AngII)-treated HK-2 cells and unilateral ureteral obstruction (UUO) in mice. Immunofluorescence staining, quantitative real-time PCR, siRNA, co-immunoprecipitation and Western blot analyses were used to evaluate expression of key molecules in RAS, Wnt/β-catenin and TGFβ/Smad pathways. Addition of the above compounds to culture media and their administration to UUO mice: (i) significantly attenuated epithelial-to-mesenchymal transition and extracellular matrix production in TGFβ1- and AngII-treated HK-2 cells and UUO mice by inhibiting Wnt/β-catenin pathway activation and Smad3 phosphorylation; (ii) selectively inhibited Smad3 phosphorylation by blocking the interaction of TGFBR1 with Smad3; and (iii) specifically inhibited Smad3 activation. PZC and PZD showed a strong inhibitory effect on all RAS components, and PZE showed a strong inhibitory effect on renin. Furthermore, the secolanostane tetracyclic triterpenoids, PZC and PZD, showed a stronger inhibitory effect than the lanostane tetracyclic triterpenoid PZE. Therefore, compounds with secolanostance skeleton showed stronger bioactivity than those with lanostance skeleton. The secolanostane tetracyclic triterpenoids effectively blocked RAS by simultaneously targeting multiple RAS components and lanostane tetracyclic triterpenoids inhibited renin and protected against tubulo-interstitial fibrosis. © 2018 The British Pharmacological Society.

Research progress on trifluoromethyl-based radical reaction process

NASA Astrophysics Data System (ADS)

Song, Hao

2017-12-01

Due to the unique properties imparted by the trifluoromethyl group, such as high electron density and strong lipotropy, which effectively improve acidity, lipophilicity and metabolic stability of the molecule itself, trifluoromethyl-substituted organic compounds are becoming increasingly important as structural motifs in pharmaceuticals, agrochemicals and organic materials. In this review, we present several methods developed for the direct introduction of a trifluoromethyl group, beginning with its rich and storied history. Then the present article addresses mechanism and process in carbon-carbon bond forming reaction based on radical process which is divided into three parts according to the way of CF3 radical generation. Finally, challenges and opportunities of researches on trifluoromethylation reactions facing are prospected.

Effect of a zinc L-carnosine compound on acid-induced injury in canine gastric mucosa ex vivo.

PubMed

Hill, Tracy L; Blikslager, Anthony T

2012-05-01

To examine whether a zinc L-carnosine compound used for treatment of suspected gastric ulcers in dogs ameliorates acid-induced injury in canine gastric mucosa. Gastric mucosa from 6 healthy dogs. Mucosa from the gastric antrum was harvested from 6 unadoptable shelter dogs immediately after euthanasia and mounted on Ussing chambers. The tissues were equilibrated for 30 minutes in neutral Ringer's solution prior to incubation with acidic Ringer's solution (HCl plus Ringer's solution [final pH, 1.5 to 2.5]), acidic Ringer's solution plus zinc L-carnosine compound, or zinc L-carnosine compound alone. Tissues were maintained for 180 minutes in Ussing chambers, during which permeability was assessed by measurement of transepithelial electrical resistance. After the 180-minute treatment period, tissues were removed from Ussing chambers and labeled with immunofluorescent anti-active caspase-3 antibody as an indicator of apoptosis. Permeability of the gastric mucosa was significantly increased in a time-dependent manner by addition of HCl, whereas control tissues maintained viability for the study period. Change in permeability was detected within the first 15 minutes after acid application and progressed over the subsequent 150 minutes. The zinc L-carnosine compound had no significant effect on this increase in permeability. Apoptosis was evident in acid-treated tissues but not in control tissues. The zinc L-carnosine compound did not protect against development of apoptosis. Addition of HCl caused a dose-dependent increase in gastric permeability over time and apparent induction of apoptosis as determined on the basis of immunofluorescence. However, there was no significant protective effect of a zinc L-carnosine compound. Nonetheless, results suggested the utility of this method for further studies of canine gastric injury.

Synthetic biology for CO2 fixation.

PubMed

Gong, Fuyu; Cai, Zhen; Li, Yin

2016-11-01

Recycling of carbon dioxide (CO 2 ) into fuels and chemicals is a potential approach to reduce CO 2 emission and fossil-fuel consumption. Autotrophic microbes can utilize energy from light, hydrogen, or sulfur to assimilate atmospheric CO 2 into organic compounds at ambient temperature and pressure. This provides a feasible way for biological production of fuels and chemicals from CO 2 under normal conditions. Recently great progress has been made in this research area, and dozens of CO 2 -derived fuels and chemicals have been reported to be synthesized by autotrophic microbes. This is accompanied by investigations into natural CO 2 -fixation pathways and the rapid development of new technologies in synthetic biology. This review first summarizes the six natural CO 2 -fixation pathways reported to date, followed by an overview of recent progress in the design and engineering of CO 2 -fixation pathways as well as energy supply patterns using the concept and tools of synthetic biology. Finally, we will discuss future prospects in biological fixation of CO 2 .

Grant Closeout Requirements and Reports

Cancer.gov

Requirements and reports to comply with grant closeout, including Final Federal Financial Report (FFR, SF425); Final Research Performance Progress Report (FRPPR); Interim Research Performance Progress Report (IRPPR); Final Invention Statement (FIS, HHS

Nitrosative stress induces DNA strand breaks but not caspase mediated apoptosis in a lung cancer cell line

PubMed Central

Bentz, Brandon G; Hammer, Neal D; Radosevich, James A; Haines, G Kenneth

2004-01-01

Background Key steps crucial to the process of tumor progression are genomic instability and escape from apoptosis. Nitric oxide and its interrelated reactive intermediates (collectively denoted as NOX) have been implicated in DNA damage and mutational events leading to cancer development, while also being implicated in the inhibition of apoptosis through S-nitrosation of key apoptotic enzymes. The purpose of this study was to explore the interrelationship between NOX-mediated DNA strand breaks (DSBs) and apoptosis in cultured tumor cell lines. Methods Two well-characterized cell lines were exposed to increasing concentrations of exogenous NOX via donor compounds. Production of NOX was quantified by the Greiss reaction and spectrophotometery, and confirmed by nitrotyrosine immunostaining. DSBs were measured by the alkaline single-cell gel electrophoresis assay (the COMET assay), and correlated with cell viability by the MTT assay. Apoptosis was analyzed both by TUNEL staining and Annexin V/propidium iodine FACS. Finally, caspase enzymatic activity was measured using an in-vitro fluorogenic caspase assay. Results Increases in DNA strand breaks in our tumor cells, but not in control fibroblasts, correlated with the concentration as well as rate of release of exogenously administered NOX. This increase in DSBs did not correlate with an increase in cell death or apoptosis in our tumor cell line. Finally, this lack of apoptosis was found to correlate with inhibition of caspase activity upon exposure to thiol- but not NONOate-based NOX donor compounds. Conclusions Genotoxicity appears to be highly interrelated with both the concentration and kinetic delivery of NOX. Moreover, alterations in cell apoptosis can be seen as a consequence of the explicit mechanisms of NOX delivery. These findings lend credence to the hypothesis that NOX may play an important role in tumor progression, and underscores potential pitfalls which should be considered when developing NOX-based chemotherapeutic agents. PMID:15617570

Clinically relevant enhancement of human sperm motility using compounds with reported phosphodiesterase inhibitor activity

PubMed Central

Tardif, Steve; Madamidola, Oladipo A.; Brown, Sean G.; Frame, Lorna; Lefièvre, Linda; Wyatt, Paul G.; Barratt, Christopher L.R.; Martins Da Silva, Sarah J.

2014-01-01

STUDY QUESTION Can we identify compound(s) with reported phosphodiesterase inhibitor (PDEI) activity that could be added to human spermatozoa in vitro to enhance their motility without compromising other sperm functions? SUMMARY ANSWER We have identified several compounds that produce robust and effective stimulation of sperm motility and, importantly, have a positive response on patient samples. WHAT IS KNOWN ALREADY For >20 years, the use of non-selective PDEIs, such as pentoxifylline, has been known to influence the motility of human spermatozoa; however, conflicting results have been obtained. It is now clear that human sperm express several different phosphodiesterases and these are compartmentalized at different regions of the cells. By using type-specific PDEIs, differential modulation of sperm motility may be achieved without adversely affecting other functions such as the acrosome reaction (AR). STUDY DESIGN, SIZE, DURATION This was a basic medical research study examining sperm samples from normozoospermic donors and subfertile patients attending the Assisted Conception Unit (ACU), Ninewells Hospital Dundee for diagnostic semen analysis, IVF and ICSI. Phase 1 screened 43 commercially available compounds with reported PDEI activity to identify lead compounds that stimulate sperm motility. Samples were exposed (20 min) to three concentrations (1, 10 and 100 µM) of compound, and selected candidates (n = 6) progressed to Phase 2, which provided a more comprehensive assessment using a battery of in vitro sperm function tests. PARTICIPANTS/MATERIALS, SETTING, METHODS All healthy donors and subfertile patients were recruited at the Medical Research Institute, University of Dundee and ACU, Ninewells Hospital Dundee (ethical approval 08/S1402/6). In Phase 1, poor motility cells recovered from the 40% interface of the discontinuous density gradient were used as surrogates for patient samples. Pooled samples from three to four different donors were utilized in order to reduce variability and increase the number of cells available for simultaneous examination of multiple compounds. During Phase 2 testing, semen samples from 23 patients attending for either routine diagnostic andrology assessment or IVF/ICSI were prepared and exposed to selected compounds. Additionally, 48 aliquots of prepared samples, surplus to clinical use, were examined from IVF (n = 32) and ICSI (n = 16) patients to further determine the effects of selected compounds under clinical conditions of treatment. Effects of compounds on sperm motility were assessed by computer-assisted sperm analysis. A modified Kremer test using methyl cellulose was used to assess sperm functional ability to penetrate into viscous media. Sperm acrosome integrity and induction of apoptosis were assessed using the acrosomal content marker PSA-FITC and annexin V kit, respectively. MAIN RESULTS AND THE ROLE OF CHANCE In Phase 1, six compounds were found to have a strong effect on poor motility samples with a magnitude of response of ≥60% increase in percentage total motility. Under capacitating and non-capacitating conditions, these compounds significantly (P ≤ 0.05) increased the percentage of total and progressive motility. Furthermore, these compounds enhanced penetration into a cervical mucus substitute (P ≤ 0.05). Finally, the AR was not significantly induced and these compounds did not significantly increase the externalization of phosphatidylserine (P = 0.6, respectively). In general, the six compounds maintained the stimulation of motility over long periods of time (180 min) and their effects were still observed after their removal. In examinations of clinical samples, there was a general observation of a more significant stimulation of sperm motility in samples with lower baseline motility. In ICSI samples, compounds #26, #37 and #38 were the most effective at significantly increasing total motility (88, 81 and 79% of samples, respectively) and progressive motility (94, 93 and 81% of samples, respectively). In conclusion, using a two-phased drug discovery screening approach including the examination of clinical samples, 3/43 compounds were identified as promising candidates for further study. LIMITATIONS, REASONS FOR CAUTION This is an in vitro study and caution must be taken when extrapolating the results. Data for patients were from one assessment and thus the robustness of responses needs to be established. The n values for ICSI samples were relatively small. WIDER IMPLICATIONS OF THE FINDINGS We have systematically screened and identified several compounds that have robust and effective stimulation (i.e. functional significance with longevity and no toxicity) of total and progressive motility under clinical conditions of treatment. These compounds could be clinical candidates with possibilities in terms of assisted reproductive technology options for current or future patients affected by asthenozoospermia or oligoasthenozoospermia. STUDY FUNDING/COMPETING INTEREST(S) This study was funded primarily by the MRC (DPFS) but with additional funding from the Wellcome Trust, Tenovus (Scotland), University of Dundee, NHS Tayside and Scottish Enterprise. The authors have no competing interests. A patent (#WO2013054111A1) has been published containing some of the information presented in this manuscript. PMID:25124668

Novel Sorafenib-Based Structural Analogues: In Vitro Anticancer Evaluation of t-MTUCB and t-AUCMB

PubMed Central

Wecksler, Aaron T.; Hwang, Sung Hee; Wettersten, Hiromi I.; Gilda, Jennifer E.; Patton, Amy; Leon, Leonardo J.; Carraway, Kermit L.; Gomes, Aldrin V.; Baar, Keith; Weiss, Robert H.; Hammock, Bruce D.

2014-01-01

In the current study, we performed a mechanistic study on the cytotoxicity of two compounds, t-AUCMB and t-MTUCB, that are structurally similar to sorafenib. These compounds display strong cytotoxic responses in various cancer cell lines, despite significant differences in the induction of apoptotic events such as caspase activation and lactate dehydrogenase release in hepatoma cells. Both compounds induce autophagosome formation and LC3I cleavage, but there was little observable effect on mTORC1 or the downstream targets, S6K1 and 4E-BP1. In addition, there was an increase in activity of upstream signaling through the IRS1/PI3K/Akt signaling pathway, suggesting that unlike sorafenib, both compounds induce mTOR-independent autophagy. The observed autophagy correlates with mitochondrial membrane depolarization, AIF release, and oxidative stress-induced glutathione depletion. However, there were no observable changes in the ER-stress markers such as, Bip, IREα, p-eIP2, and the lipid peroxidation marker, 4-HNE, suggesting ER-independent oxidative stress. Finally, these compounds do not possess the multikinase inhibitory activity of sorafenib, which may be reflected in their difference in ability to halt cell cycle progression compared to sorafenib. Our findings indicate that both compounds have anti-cancer effects comparable to sorafenib in multiple cell line, but they induce significant differences in apoptotic responses and appear to induce mTOR-independent autophagy. t-AUCMB and t-MTUCB, represent novel chemical probes that are capable of inducing mTOR-independent autophagy and apoptosis to differing degrees, and thus may be potential tools for further understanding the link between these two cellular stress responses. PMID:24525589

A comparative bear model for immobility-induced osteopenia

NASA Technical Reports Server (NTRS)

Milbury, P. E.; Vaughan, M. R.; Farley, S.; Matula, G. J. Jr; Convertino, V. A.; Matson, W. R.

1998-01-01

The National Institutes of Health (NIH) and the National Aeronautics and Space Administration (NASA) are seeking solutions to the human problem of osteopenia, or immobility-induced bone loss. Bears, during winter dormancy, appear uniquely exempted from the debilitating effects of immobility osteopenia. NIH and ESA, Inc. are creating a large database of metabolic information on human ambulatory and bedrest plasma samples for comparison with metabolic data obtained from bear plasma samples collected in different seasons. The database generated from NASA's HR113 human bedrest study showed a clear difference between plasma samples of ambulatory and immobile subjects through cluster analysis using compounds determined by high performance liquid chromatography with coulometric electrochemical array detection (HPLC-EC). We collected plasma samples from black bears (Ursus americanus) across 4 seasons and from 3 areas and subjected them to similar analysis, with particular attention to compounds that changed significantly in the NASA human study. We found seasonal differences in 28 known compounds and 33 unknown compounds. A final database contained 40 known and 120 unknown peaks that were reliably assayed in all bear and human samples; these were the primary data set for interspecies comparison. Six unidentified compounds changed significantly but differentially in wintering bears and immobile humans. The data are discussed in light of current theories regarding dormancy, starvation, and anabolic metabolism. Work is in progress by ESA Laboratories on a larger database to confirm these findings prior to a chemical isolation and identification effort. This research could lead to new pharmaceuticals or dietary interventions for the treatment of immobility osteopenia.

Treatment of Mycobacterium intracellulare Infected Mice with Walter Reed Compound H

DTIC Science & Technology

1980-09-25

including Mycobacterium tuberculosis, Mycobacterium leprae , Staphylococcusaureus, Pseudomonas aeruginosa, Escherichia coli, enterococ----ci, Neissr•~n...97 SAD "Treatment of Mycobacterium intracellulare Infected Mice with Walter Reed Compound H" Final Comprehensive Report J. Kenneth McClatchy, Ph.D...REPORT & PERIOD COVERED "TREATMENT OF MYCOBACTERIUM INTRACELLULARE - Final Comprehensive Report INFECTED MICE WITH WALTER REED COMPOUND H"li G

[Analysis of projects funded by NSFC in field of Chinese material medica resource in recent three years].

PubMed

Gao, Wei; Guo, Shu-Zhen; Han, Li-Wei; Zhang, Feng-Zhu

2016-10-01

The paper reviewed the sponsorship and final reports of projects focus on Science of Chinese materia medica resource in Medical Science Department, National Natural Science Foundation of China. The applicant and supportive organizations were analyzed. The progress and results of some projects were summarized by research fields including formation mechanism of Dao-di herbs, research of plant taxonomy, breeding and cultivation of medical plants, ecological and environmental adaptability of Chinese materia medica resource, quality assessment of Chinese materia medica resource, and biosynthesis and regulation of active compounds. In addition, the potential problems and the most and least focused areas in the application were summarized for reference. Copyright© by the Chinese Pharmaceutical Association.

Populational divergence in the impact of three nitrogenous compounds and their combination on larvae of the frog Pelophylax perezi (Seoane, 1885).

PubMed

Egea-Serrano, Andrés; Tejedo, Miguel; Torralva, Mar

2009-08-01

Pollution by nitrogenous compounds is a putative stressful factor that may be causally linked to the decline of amphibians. One way to understand the potentially detrimental consequences of eutrophication on amphibian populations is to investigate variation among populations differing in exposure to nitrogen, this variation potentially indicating evolutionary potential to cope with this stressor. We have examined the effect of nitrogenous compounds (NH(4)(+); NO(2)(-); NO(3)(-), both alone and in combination) on fitness-related larval traits in four populations of Pelophylax perezi naturally exposed to different degrees of eutrophication. The results indicate that both survival and larval final size decrease at higher concentrations of these compounds, either singly or in combination. Additionally, the nitrogenous compounds were more lethal and larval food consumption and final mass were significantly reduced when they were exposed to combinations of compounds. Populations inhabiting highly polluted aquatic environments tolerated higher levels of nitrogenous compounds and showed higher survival rates and larger final size than the populations of less polluted environments, suggesting the potential to adapt to increased nitrogenous contamination in this species.

Plants and their bioactive compounds with the potential to enhance mechanisms of inherited cardiac regeneration.

PubMed

Zhou, Zhen; Li, Dianbin; Zhou, Hua; Lin, Xiaoli; Li, Censing; Tang, Mingfeng; Feng, Zhou; Li, Ming

2015-06-01

This article reviews the current progress and research indications in the application of natural plant compounds with the potential for the treatment of cardiovascular diseases. Our understanding of how to apply natural plant compounds to enhance mechanisms of inherited cardiac regeneration, which is physiologically pertinent to myocyte turnover or minor cardiac repair, for substantial cardiac regeneration to repair pathological heart injuries is discussed. Although significant progress has been made in the application of natural plant compounds for therapy of heart diseases, the understanding or the application of these compounds specifically for enhancing mechanisms of inherited cardiac regeneration for the treatment of cardiovascular diseases is little. Recent recognition of some natural plant compounds that can repair damaged myocardial tissues through enhancing mechanisms of inherited cardiac regeneration has offered an alternative for clinical translation. Application of natural plant compounds, which show the activity of manipulating gene expressions in such a way to enhance mechanisms of inherited cardiac regeneration for cardiac repair, may provide a promising strategy for the reconstruction of damaged cardiac tissues due to cardiovascular diseases. Georg Thieme Verlag KG Stuttgart · New York.

Analyzing compound and project progress through multi-objective-based compound quality assessment.

PubMed

Nissink, J Willem M; Degorce, Sébastien

2013-05-01

Compound-quality scoring methods designed to evaluate multiple drug properties concurrently are useful to analyze and prioritize output from drug-design efforts. However, formalized multiparameter optimization approaches are not widely used in drug design. We rank molecules synthesized in drug-discovery projects using simple and aggregated desirability functions reflecting medicinal chemistry 'rules'. Our quality score deals transparently with missing data, a key requirement in drug-hunting projects where data availability is often limited. We further estimate confidence in the interpretation of such a compound-quality measure. Scores and associated confidences provide systematic insight in the quality of emerging chemical equity. Tracking quality of synthetic output over time yields valuable insight into the progress of drug-design teams, with potential applications in risk and resource management of a drug portfolio.

Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression.

PubMed

Feng, Shu; Shao, Longjiang; Yu, Wendong; Gavine, Paul; Ittmann, Michael

2012-07-15

Extensive correlative studies in human prostate cancer as well as studies in vitro and in mouse models indicate that fibroblast growth factor receptor (FGFR) signaling plays an important role in prostate cancer progression. In this study, we used a probe compound for an FGFR inhibitor, which potently inhibits FGFR-1-3 and significantly inhibits FGFR-4. The purpose of this study is to determine whether targeting FGFR signaling from all four FGFRs will have in vitro activities consistent with inhibition of tumor progression and will inhibit tumor progression in vivo. Effects of AZ8010 on FGFR signaling and invasion were analyzed using immortalized normal prostate epithelial (PNT1a) cells and PNT1a overexpressing FGFR-1 or FGFR-4. The effect of AZ8010 on invasion and proliferation in vitro was also evaluated in prostate cancer cell lines. Finally, the impact of AZ8010 on tumor progression in vivo was evaluated using a VCaP xenograft model. AZ8010 completely inhibits FGFR-1 and significantly inhibits FGFR-4 signaling at 100 nmol/L, which is an achievable in vivo concentration. This results in marked inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and invasion in PNT1a cells expressing FGFR-1 and FGFR-4 and all prostate cancer cell lines tested. Treatment in vivo completely inhibited VCaP tumor growth and significantly inhibited angiogenesis and proliferation and increased cell death in treated tumors. This was associated with marked inhibition of ERK phosphorylation in treated tumors. Targeting FGFR signaling is a promising new approach to treating aggressive prostate cancer.

Can Intestinal Phosphate Binding or Inhibition of Hydroxyapatite Growth in the Vascular Wall Halt the Progression of Established Aortic Calcification in Chronic Kidney Disease?

PubMed

Neven, Ellen; Opdebeeck, Britt; De Maré, Annelies; Bashir-Dar, Rida; Dams, Geert; Marynissen, Rita; Behets, Geert J; Verhulst, Anja; Riser, Bruce L; D'Haese, Patrick C

2016-11-01

Vascular calcification significantly contributes to mortality in chronic kidney disease (CKD) patients. Sevelamer and pyrophosphate (PPi) have proven to be effective in preventing vascular calcification, the former by controlling intestinal phosphate absorption, the latter by directly interfering with the hydroxyapatite crystal formation. Since most patients present with established vascular calcification, it is important to evaluate whether these compounds may also halt or reverse the progression of preexisting vascular calcification. CKD and vascular calcification were induced in male Wistar rats by a 0.75 % adenine low protein diet for 4 weeks. Treatment with PPi (30 or 120 µmol/kg/day), sevelamer carbonate (1500 mg/kg/day) or vehicle was started at the time point at which vascular calcification was present and continued for 3 weeks. Hyperphosphatemia and vascular calcification developed prior to treatment. A significant progression of aortic calcification in vehicle-treated rats with CKD was observed over the final 3-week period. Sevelamer treatment significantly reduced further progression of aortic calcification as compared to the vehicle control. No such an effect was seen for either PPi dose. Sevelamer but not PPi treatment resulted in an increase in both osteoblast and osteoid perimeter. Our study shows that sevelamer was able to reduce the progression of moderate to severe preexisting aortic calcification in a CKD rat model. Higher doses of PPi may be required to induce a similar reduction of severe established arterial calcification in this CKD model.

USSR Report, Chemistry

DTIC Science & Technology

1984-01-06

Sep-Oct 83) ................................. ANALYTICAL CHEMISTRY Ionometric Determination of Copper in Organic Compounds S(S. L. Davydova, et al...Committee Reviews Progress in Fertilizer Industry (EKONOMICHESKAYA GAZETA, No 42, Oct 83) .................. 30 INORGANIC COMPOUNDS Speed of Ultrasound...Sep 83).. ........... .......... . . .. . . . . .... 39 NITROGEN COMPOUNDS Phototropy of Quaternary Ammonium Salts of N,N’-Bis- Substituted Diimides

Role of Forkhead Box Class O proteins in cancer progression and metastasis.

PubMed

Kim, Chang Geun; Lee, Hyemin; Gupta, Nehal; Ramachandran, Sharavan; Kaushik, Itishree; Srivastava, Sangeeta; Kim, Sung-Hoon; Srivastava, Sanjay K

2018-06-01

It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3 K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far. Thus, with previous experimental evidences, the present review discussed the role of FoxOs in association with metastasis related molecules including cannabinoid receptor 1 (CNR1), Cdc25A/Cdk2, Src, serum and glucocorticoid inducible kinases (SGKs), CXCR4, E-cadherin, annexin A8 (ANXA8), Zinc finger E-box-binding homeobox 2 (ZEB2), human epidermal growth factor receptor 2 (HER2) and mRNAs such as miR-182, miR-135b, miR-499-5p, miR-1274a, miR-150, miR-34b/c and miR-622, subsequently analyzed the molecular mechanism of some natural compounds targeting FoxOs and finally suggested future research directions in cancer progression and metastasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel microtubule-targeted agent 6-chloro-4-(methoxyphenyl) coumarin induces G2-M arrest and apoptosis in HeLa cells

PubMed Central

Ma, Yi-ming; Zhou, Yu-bo; Xie, Chuan-ming; Chen, Dong-mei; Li, Jia

2012-01-01

Aim: To identify a novel coumarin analogue with the highest anticancer activity and to further investigate its anticancer mechanisms. Methods: The viability of cancer cells was investigated using the MTT assay. The cell cycle progression was evaluated using both flow cytometric and Western blotting analysis. Microtubule depolymerization was observed with immunocytochemistry in vivo and a tubulin depolymerization assay in vitro. Apoptosis was demonstrated using Annexin V/Propidium Iodide (PI) double-staining and sub-G1 analysis. Results: Among 36 analogues of coumarin, 6-chloro-4-(methoxyphenyl) coumarin showed the best anticancer activity (IC50 value about 200 nmol/L) in HCT116 cells. The compound had a broad spectrum of anticancer activity against 9 cancer cell lines derived from colon cancer, breast cancer, liver cancer, cervical cancer, leukemia, epidermoid cancer with IC50 value of 75 nmol/L–1.57 μmol/L but with low cytotocitity against WI-38 human lung fibroblasts (IC50 value of 12.128 μmol/L). The compound (0.04–10 μmol/L) induced G2-M phase arrest in HeLa cells in a dose-dependent manner, which was reversible after the compound was removed. The compound (10–300 μmol/L) induced the depolymerization of purified porcine tubulin in vitro. Finally, the compound (0.04–2.5 μmol/L) induced apoptosis of HeLa cells in dose- and time-dependent manners. Conclusion: 6-Chloro-4-(methoxyphenyl) coumarin is a novel microtubule-targeting agent that induces G2–M arrest and apoptosis in HeLa cells. PMID:22266726

In silico probing and biological evaluation of SETDB1/ESET-targeted novel compounds that reduce tri-methylated histone H3K9 (H3K9me3) level

NASA Astrophysics Data System (ADS)

Park, Insun; Hwang, Yu Jin; Kim, TaeHun; Viswanath, Ambily Nath Indu; Londhe, Ashwini M.; Jung, Seo Yun; Sim, Kyoung Mi; Min, Sun-Joon; Lee, Ji Eun; Seong, Jihye; Kim, Yun Kyung; No, Kyoung Tai; Ryu, Hoon; Pae, Ae Nim

2017-10-01

ERG-associated protein with the SET domain (ESET/SET domain bifurcated 1/SETDB1/KMT1E) is a histone lysine methyltransferase (HKMT) and it preferentially tri-methylates lysine 9 of histone H3 (H3K9me3). SETDB1/ESET leads to heterochromatin condensation and epigenetic gene silencing. These functional changes are reported to correlate with Huntington's disease (HD) progression and mood-related disorders which make SETDB1/ESET a viable drug target. In this context, the present investigation was performed to identify novel peptide-competitive small molecule inhibitors of the SETDB1/ESET by a combined in silico-in vitro approach. A ligand-based pharmacophore model was built and employed for the virtual screening of ChemDiv and Asinex database. Also, a human SETDB1/ESET homology model was constructed to supplement the data further. Biological evaluation of the selected 21 candidates singled out 5 compounds exhibiting a notable reduction of the H3K9me3 level via inhibitory potential of SETDB1/ESET activity in SETDB1/ESET-inducible cell line and HD striatal cells. Later on, we identified two compounds as final hits that appear to have neuronal effects without cytotoxicity based on the result from MTT assay. These compounds hold the calibre to become the future lead compounds and can provide structural insights into more SETDB1/ESET-focused drug discovery research. Moreover, these SETDB1/ESET inhibitors may be applicable for the preclinical study to ameliorate neurodegenerative disorders via epigenetic regulation.

In silico probing and biological evaluation of SETDB1/ESET-targeted novel compounds that reduce tri-methylated histone H3K9 (H3K9me3) level.

PubMed

Park, Insun; Hwang, Yu Jin; Kim, TaeHun; Viswanath, Ambily Nath Indu; Londhe, Ashwini M; Jung, Seo Yun; Sim, Kyoung Mi; Min, Sun-Joon; Lee, Ji Eun; Seong, Jihye; Kim, Yun Kyung; No, Kyoung Tai; Ryu, Hoon; Pae, Ae Nim

2017-10-01

ERG-associated protein with the SET domain (ESET/SET domain bifurcated 1/SETDB1/KMT1E) is a histone lysine methyltransferase (HKMT) and it preferentially tri-methylates lysine 9 of histone H3 (H3K9me3). SETDB1/ESET leads to heterochromatin condensation and epigenetic gene silencing. These functional changes are reported to correlate with Huntington's disease (HD) progression and mood-related disorders which make SETDB1/ESET a viable drug target. In this context, the present investigation was performed to identify novel peptide-competitive small molecule inhibitors of the SETDB1/ESET by a combined in silico-in vitro approach. A ligand-based pharmacophore model was built and employed for the virtual screening of ChemDiv and Asinex database. Also, a human SETDB1/ESET homology model was constructed to supplement the data further. Biological evaluation of the selected 21 candidates singled out 5 compounds exhibiting a notable reduction of the H3K9me3 level via inhibitory potential of SETDB1/ESET activity in SETDB1/ESET-inducible cell line and HD striatal cells. Later on, we identified two compounds as final hits that appear to have neuronal effects without cytotoxicity based on the result from MTT assay. These compounds hold the calibre to become the future lead compounds and can provide structural insights into more SETDB1/ESET-focused drug discovery research. Moreover, these SETDB1/ESET inhibitors may be applicable for the preclinical study to ameliorate neurodegenerative disorders via epigenetic regulation.

Marine Polysaccharides in Pharmaceutical Applications: An Overview

PubMed Central

Laurienzo, Paola

2010-01-01

The enormous variety of polysaccharides that can be extracted from marine plants and animal organisms or produced by marine bacteria means that the field of marine polysaccharides is constantly evolving. Recent advances in biological techniques allow high levels of polysaccharides of interest to be produced in vitro. Biotechnology is a powerful tool to obtain polysaccharides from a variety of micro-organisms, by controlling the growth conditions in a bioreactor while tailoring the production of biologically active compounds. Following an overview of the current knowledge on marine polysaccharides, with special attention to potential pharmaceutical applications and to more recent progress on the discovering of new polysaccharides with biological appealing characteristics, this review will focus on possible strategies for chemical or physical modification aimed to tailor the final properties of interest. PMID:20948899

Recent Advances in Nanostructured Thermoelectric Half-Heusler Compounds

PubMed Central

Xie, Wenjie; Weidenkaff, Anke; Tang, Xinfeng; Zhang, Qingjie; Poon, Joseph; Tritt, Terry M.

2012-01-01

Half-Heusler (HH) alloys have attracted considerable interest as promising thermoelectric (TE) materials in the temperature range around 700 K and above, which is close to the temperature range of most industrial waste heat sources. The past few years have seen nanostructuing play an important role in significantly enhancing the TE performance of several HH alloys. In this article, we briefly review the recent progress and advances in these HH nanocomposites. We begin by presenting the structure of HH alloys and the different strategies that have been utilized for improving the TE properties of HH alloys. Next, we review the details of HH nanocomposites as obtained by different techniques. Finally, the review closes by highlighting several promising strategies for further research directions in these very promising TE materials. PMID:28348315

Thermal and Kinetic Modelling of Elastomer Flow—Application to an Extrusion Die

NASA Astrophysics Data System (ADS)

Launay, J.; Allanic, N.; Mousseau, P.; Deterre, R.

2011-05-01

This paper reports and discusses the thermal and kinetic behaviour of elastomer flow inside an extrusion die. The reaction progress through the runner was modeled by using a particle tracking technique. The aim is to analyze viscous dissipation phenomena to control scorch arisen, improve the rubber compound curing homogeneity and reduce the heating time in the mould using the progress of the induction time. The heat and momentum equations were solved in three dimensions with Ansys Polyflow. A particle tracking technique was set up to calculate the reaction progress. Several simulations were performed to highlight the influence of process parameters and geometry modifications on the rubber compound thermal and cure homogeneity.

Are We There Yet? Applying Thermodynamic and Kinetic Profiling on Embryonic Ectoderm Development (EED) Hit-to-Lead Program.

PubMed

Wang, Ying; Edalji, Rohinton P; Panchal, Sanjay C; Sun, Chaohong; Djuric, Stevan W; Vasudevan, Anil

2017-10-26

It is advocated that kinetic and thermodynamic profiling of bioactive compounds should be incorporated and utilized as complementary tools for hit and lead optimizations in drug discovery. To assess their applications in the EED hit-to-lead optimization process, large amount of thermodynamic and kinetic data were collected and analyzed via isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR), respectively. Slower dissociation rates (k off ) of the lead compounds were observed as the program progressed. Analysis of the kinetic data indicated that compound cellular activity correlated with both K i and k off . Our analysis revealed that ITC data should be interpreted in the context of chiral purity of the compounds. The thermodynamic signatures of the EED aminopyrrolidine compounds were found to be mainly enthalpy driven with improved enthalpic contributions as the program progressed. Our study also demonstrated that significant challenges still exist in utilizing kinetic and thermodynamic parameters for hit selection.

Proposed Oral Reference Dose (RfD) for Barium and Compounds (Final Report, 2004)

EPA Science Inventory

This document is the final report from the 2004 external peer review of the Proposed Oral Reference Dose (RfD) for Barium and Compounds, prepared by the U.S. Environmental Protection Agency (EPA), National Center for Environmental Assessment (NCEA), for the Integrated Risk...

Evaluation of epoxy compounds as a material for patching and protecting concrete : final report.

DOT National Transportation Integrated Search

1971-01-01

The final report summarizes the results of a study of the use of epoxy compounds in the shallow surface repair and sealing of concrete bridge decks. The research effort concentrated on the use of epoxy resin systems as bonded overlays and included ev...

Social Reconstructionism or Child-Centered Progressivism? Difficulties Defining Progressive Education from the PEA's 1939 Documentary Film, School

ERIC Educational Resources Information Center

Kridel, Craig

2013-01-01

In "The Transformation of the School", Lawrence Cremin warned against formulating any capsule definition of progressive education: "None exists, and none ever will; for throughout its history progressive education meant different things to different people, and these differences were only compounded by the remarkable diversity of…

Progress in the field of physiologically active lanosterol compounds

NASA Astrophysics Data System (ADS)

Reshetova, I. G.; Tkhaper, R. K.; Kamernitskii, Alexey V.

1992-08-01

This review correlates the studies (up to 1991) on the isolation, structural determination, biological activity, and synthesis of physiologically active polyoxidised lanosterol derivatives of vegetable (inotodiol, ganoderic acids) and animal (seychellogenin) origin. The cytotoxic, cardiovascular, and other forms of activity of compounds of this type are of considerable interest in relation to their medical use. It is noted that the functionalised side chain (in an open form or containing lactones, lactols, etc.) is generally responsible for the activity exhibited by lanosterol derivatives. Two basic approaches to the derivation of these structures are defined: either by complete reconstruction of the side chain of lanosterol (degradation and rebuilding with oxygen-containing residues) or by progressive functionalisation of the Δ24-side chain of lanosterol. The synthesis of the known anticancer compound "inotodiol", seychellogenins, ganoderic acids, and other compounds are described. The bibliography includes 105 references.

Fabrication and Testing of High-Speed-Single-Rotor and Compound-Rotor Systems

DTIC Science & Technology

2016-05-04

pitch link loads, hub loads, rotor wakes and performance of high -speed single-rotor and compound-rotor systems to support 1. REPORT DATE (DD-MM-YYYY) 4...Public Release; Distribution Unlimited UU UU UU UU 05-04-2016 14-Jul-2014 13-Jan-2016 Final Report: Fabrication and Testing of High -Speed Single- Rotor and...Final Report: Fabrication and Testing of High -Speed Single-Rotor and Compound-Rotor Systems Report Title The Alfred Gessow Rotorcraft Center has

Fabrication and Testing of High-Speed Single-Rotor and Compound-Rotor Systems

DTIC Science & Technology

2016-04-05

pitch link loads, hub loads, rotor wakes and performance of high -speed single-rotor and compound-rotor systems to support 1. REPORT DATE (DD-MM-YYYY) 4...Public Release; Distribution Unlimited UU UU UU UU 05-04-2016 14-Jul-2014 13-Jan-2016 Final Report: Fabrication and Testing of High -Speed Single- Rotor and...Final Report: Fabrication and Testing of High -Speed Single-Rotor and Compound-Rotor Systems Report Title The Alfred Gessow Rotorcraft Center has

Organometallic chemistry of heterobimetallic compounds: Final report for the period August 1, 1985-June 30, 1988

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

Casey, C.P.

1988-03-01

Work is reported on the following: formyl compounds, cyclopentadienyl ring slippage, ..mu..-hydrocarbyl diiron complexes, heterobimetallic compounds linked by heterodifunctional ligands, heterobimetallic dihydrides, reactions of heterobimetallic dihydrides, early-late transition metal bimetallic compounds, and heterobimetallic ..mu..-alkylidene complexes. (DLC)

The geochemical and genetic role of organic substances in postmagmatic derivatives of alkaline plutons

NASA Astrophysics Data System (ADS)

Ermolaeva, V. N.; Chukanov, N. V.; Pekov, I. V.; Kogarko, L. N.

2009-12-01

Solid bituminous substances (SBS) are common components of the late hydrothermal mineral assemblages of peralkaline pegmatites. SBS are formed in a reductive setting as a result of progressive sorption of minor carbon-bearing molecules (CO, CO2, CH4, C2H6, C2H4, etc.), their polymerization, transformation into aromatic compounds (reformation), and selective oxidation on microporous zeolite-like Ti-, Nb-, and Zrsilicates serving as sorbents and catalysts. The oxygen-bearing aromatic compounds with hydrophile functional groups (-OH, -C=O, -COOH, -COO) act as complexing agents with respect to Th, REE, U, Zr, Ti, Nb, Ba, Sr, Ca, resulting in transfer of these bitumenophile elements under low-temperature hydrothermal conditions in the form of water-soluble macroassociates of the micelle type. Th, REE, and to a lesser extent, U, Zr, Ti, and Nb concentrate at the late stage of the hydrothermal process as microphases impregnating SBS or macroscopic segregations of Th and REE minerals. At the final stage, homogeneous SBS break down into organic (partly together with Ca, Sr, Ba, and Pb) and mineral (with Th, Ln, Y, Ti, Nb, Ca, Na, K, Si) microphases.

A Nonsecosteroidal Vitamin D Receptor Modulator Ameliorates Experimental Autoimmune Encephalomyelitis without Causing Hypercalcemia

PubMed Central

Na, Songqing; Ma, Yanfei; Zhao, Jingyong; Schmidt, Clint; Zeng, Qing Q.; Chandrasekhar, Srinivasan; Chin, William W.; Nagpal, Sunil

2011-01-01

Vitamin D receptor (VDR) agonists are currently the agents of choice for the treatment of psoriasis, a skin inflammatory indication that is believed to involve an autoimmune component. 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active metabolite of vitamin D, has shown efficacy in animal autoimmune disease models of multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and type I diabetes. However, the side effect of 1,25-(OH)2D3 and its synthetic secosteroidal analogs is hypercalcemia, which is a major impediment in their clinical development for autoimmune diseases. Hypercalcemia develops as a result of the action of VDR agonists on the intestine. Here, we describe the identification of a VDR modulator (VDRM) compound A that was transcriptionally less active in intestinal cells and as a result exhibited less calcemic activity in vivo than 1,25-(OH)2D3. Cytokine analysis indicated that the VDRM not only modulated the T-helper cell balance from Th1 to Th2 effector function but also inhibited Th17 differentiation. Finally, we demonstrate that the oral administration of compound A inhibited the induction and progress of experimental autoimmune encephalomyelitis in mice without causing hypercalcemia. PMID:21318047

Novel Transition Metal Compounds with Promising Thermoelectric Properties

NASA Technical Reports Server (NTRS)

Caillat, T.; Borshchevsky, A.; Fleurial, J. -P.

1993-01-01

Progress in the search for new high temperature thermoelectric materials at the Jet Propulsion Laboratory is reviewed. Novel transition metal compounds were selected as potential new high performance thermoelectric materials and criteria of selection are presented and discussed. Samples of these new compounds were prepared at JPL by a variety of techniques. Encouraging experimental results obtained on several of these compounds are reported and show that they have the potential to be the next generation of thermoelectric materials.

Final Progress Report for Ionospheric Dusty Plasma In the Laboratory [Smokey Plasma

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

Robertson, Scott

2010-07-31

“Ionospheric Dusty Plasma in the Laboratory” is a research project with the purpose of finding and reproducing the characteristics of plasma in the polar mesosphere that is unusually cold (down to 140 K) and contains nanometer-sized dust particles. This final progress report summarizes results from four years of effort that include a final year with a no-cost extension.

Chemical Conversions of Biomass-Derived Platform Chemicals over Copper-Silica Nanocomposite Catalysts.

PubMed

Upare, Pravin P; Hwang, Young Kyu; Lee, Jong-Min; Hwang, Dong Won; Chang, Jong-San

2015-07-20

Biomass and biomass-derived carbohydrates have a high extent of functionality, unlike petroleum, which has limited functionality. In biorefinery applications, the development of methods to control the extent of functionality in final products intended for use as fuels and chemicals is a challenge. In the chemical industry, heterogeneous catalysis is an important tool for the defunctionalization of functionalized feedstocks and biomass-derived platform chemicals to produce value-added chemicals. Herein, we review the recent progress in this field, mainly of vapor phase chemical conversion of biomass-derived C4 -C6 carboxylic acids and esters using copper-silica nanocomposite catalysts. We also demonstrate that these nanocomposite catalysts very efficiently convert biomass-derived platform chemicals into cyclic compounds, such as lactones and hydrofurans, with high selectivities and yields. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pharmacologic inhibition of the menin-MLL interaction blocks progression of MLL leukemia in vivo

DOE PAGES

Borkin, Dmitry; He, Shihan; Miao, Hongzhi; ...

2015-03-26

Chromosomal translocations affecting mixed lineage leukemia gene ( MLL) result in acute leukemias resistant to therapy. The leukemogenic activity of MLL fusion proteins is dependent on their interaction with menin, providing basis for therapeutic intervention. In this paper, we report the development of highly potent and orally bioavailable small-molecule inhibitors of the menin-MLL interaction, MI-463 and MI-503, and show their profound effects in MLL leukemia cells and substantial survival benefit in mouse models of MLL leukemia. Finally, we demonstrate the efficacy of these compounds in primary samples derived from MLL leukemia patients. In conclusion, overall, we demonstrate that pharmacologic inhibitionmore » of the menin-MLL interaction represents an effective treatment for MLL leukemias in vivo and provide advanced molecular scaffold for clinical lead identification.« less

Detection Progress of Selected Drugs in TLC

PubMed Central

Pyka, Alina

2014-01-01

This entry describes applications of known indicators and dyes as new visualizing reagents and various visualizing systems as well as photocatalytic reactions and bioautography method for the detection of bioactive compounds including drugs and compounds isolated from herbal extracts. Broadening index, detection index, characteristics of densitometric band, modified contrast index, limit of detection, densitometric visualizing index, and linearity range of detected compounds were used for the evaluation of visualizing effects of applied visualizing reagents. It was shown that visualizing effect depends on the chemical structure of the visualizing reagent, the structure of the substance detected, and the chromatographic adsorbent applied. The usefulness of densitometry to direct detection of some drugs was also shown. Quoted papers indicate the detection progress of selected drugs investigated by thin-layer chromatography (TLC). PMID:24551853

Sequential chemical-biological processes for the treatment of industrial wastewaters: review of recent progresses and critical assessment.

PubMed

Guieysse, Benoit; Norvill, Zane N

2014-02-28

When direct wastewater biological treatment is unfeasible, a cost- and resource-efficient alternative to direct chemical treatment consists of combining biological treatment with a chemical pre-treatment aiming to convert the hazardous pollutants into more biodegradable compounds. Whereas the principles and advantages of sequential treatment have been demonstrated for a broad range of pollutants and process configurations, recent progresses (2011-present) in the field provide the basis for refining assessment of feasibility, costs, and environmental impacts. This paper thus reviews recent real wastewater demonstrations at pilot and full scale as well as new process configurations. It also discusses new insights on the potential impacts of microbial community dynamics on process feasibility, design and operation. Finally, it sheds light on a critical issue that has not yet been properly addressed in the field: integration requires complex and tailored optimization and, of paramount importance to full-scale application, is sensitive to uncertainty and variability in the inputs used for process design and operation. Future research is therefore critically needed to improve process control and better assess the real potential of sequential chemical-biological processes for industrial wastewater treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Bax/Tubulin/Epithelial-Mesenchymal Pathways Determine the Efficacy of Silybin Analog HM015k in Colorectal Cancer Cell Growth and Metastasis.

PubMed

Amawi, Haneen; Hussein, Noor A; Ashby, Charles R; Alnafisah, Rawan; Sanglard, Leticia M; Manivannan, Elangovan; Karthikeyan, Chandrabose; Trivedi, Piyush; Eisenmann, Kathryn M; Robey, Robert W; Tiwari, Amit K

2018-01-01

The inhibition of apoptosis, disruption of cellular microtubule dynamics, and over-activation of the epithelial mesenchymal transition (EMT), are involved in the progression, metastasis, and resistance of colorectal cancer (CRC) to chemotherapy. Therefore, the design of a molecule that can target these pathways could be an effective strategy to reverse CRC progression and metastasis. In this study, twelve novel silybin derivatives, HM015a-HM015k (15a-15k) and compound 17, were screened for cytotoxicity in CRC cell lines. Compounds HM015j and HM015k (15k and 15j) significantly decreased cell proliferation, inhibited colony formation, and produced cell cycle arrest in CRC cells. Furthermore, 15k significantly induced the formation of reactive oxygen species and apoptosis. It induced the cleavage of the intrinsic apoptotic protein (Bax p21) to its more efficacious fragment, p18. Compound 15k also inhibited tubulin expression and disrupted its structure. Compound 15k significantly decreased metastatic LOVO cell migration and invasion. Furthermore, 15k reversed mesenchymal morphology in HCT116 and LOVO cells. Additionally, 15k significantly inhibited the expression of the mesenchymal marker N-cadherin and upregulated the expression of the epithelial marker, E-cadherin. Compound 15k inhibited the expression of key proteins known to induce EMT (i.e., DVL3, β-catenin, c-Myc) and upregulated the anti-metastatic protein, cyclin B1. Overall, in vitro , 15k significantly inhibited CRC progression and metastasis by inhibiting apoptosis, tubulin activity and the EMT pathways. Overall, these data suggest that compound 15k should be tested in vivo in a CRC animal model for further development.

Target identification of small molecules based on chemical biology approaches.

PubMed

Futamura, Yushi; Muroi, Makoto; Osada, Hiroyuki

2013-05-01

Recently, a phenotypic approach-screens that assess the effects of compounds on cells, tissues, or whole organisms-has been reconsidered and reintroduced as a complementary strategy of a target-based approach for drug discovery. Although the finding of novel bioactive compounds from large chemical libraries has become routine, the identification of their molecular targets is still a time-consuming and difficult process, making this step rate-limiting in drug development. In the last decade, we and other researchers have amassed a large amount of phenotypic data through progress in omics research and advances in instrumentation. Accordingly, the profiling methodologies using these datasets expertly have emerged to identify and validate specific molecular targets of drug candidates, attaining some progress in current drug discovery (e.g., eribulin). In the case of a compound that shows an unprecedented phenotype likely by inhibiting a first-in-class target, however, such phenotypic profiling is invalid. Under the circumstances, a photo-crosslinking affinity approach should be beneficial. In this review, we describe and summarize recent progress in both affinity-based (direct) and phenotypic profiling (indirect) approaches for chemical biology target identification.

Systematic Analysis of Cell Cycle Effects of Common Drugs Leads to the Discovery of a Suppressive Interaction between Gemfibrozil and Fluoxetine

PubMed Central

Hoose, Scott A.; Duran, Camille; Malik, Indranil; Eslamfam, Shabnam; Shasserre, Samantha C.; Downing, S. Sabina; Hoover, Evelyn M.; Dowd, Katherine E.; Smith, Roger; Polymenis, Michael

2012-01-01

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation. PMID:22567160

Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.

PubMed

Hoose, Scott A; Duran, Camille; Malik, Indranil; Eslamfam, Shabnam; Shasserre, Samantha C; Downing, S Sabina; Hoover, Evelyn M; Dowd, Katherine E; Smith, Roger; Polymenis, Michael

2012-01-01

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation.

Assessment of chimeric mice with humanized livers in new drug development: generation of pharmacokinetics, metabolism and toxicity data for selecting the final candidate compound.

PubMed

Kamimura, Hidetaka; Ito, Satoshi

2016-01-01

1. Chimeric mice with humanized livers are expected to be a novel tool for new drug development. This review discusses four applications where these animals can be used efficiently to collect supportive data for selecting the best compound in the final stage of drug discovery. 2. The first application is selection of the final compound based on estimated pharmacokinetic parameters in humans. Since chimeric mouse livers are highly repopulated with human hepatocytes, hepatic clearance values in vivo could be used preferentially to estimate pharmacokinetic profiles for humans. 3. The second is prediction of human-specific or disproportionate metabolites. Chimeric mice reproduce human-specific metabolites of drugs under development to conform to ICH guidance M3(R2), except for compounds that were extensively eliminated by co-existing mouse hepatocytes. 4. The third is identifying metabolites with distinct pharmacokinetic profiles in humans. Slow metabolite elimination specifically in humans increases its exposure level, but if its elimination is faster in laboratory animals, the animal exposure level might not satisfy ICH guidance M3(R2). 5. Finally, two examples of reproducing acute liver toxicity in chimeric mice are introduced. Integrated pharmacokinetics, metabolism and toxicity information are expected to assist pharmaceutical scientists in selecting the best candidate compound in new drug development.

PSI-Center Final Progress Report

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

Jarboe, Thomas R.; Shumlak, Uri; Sovinec, Carl

This is the Final Progress Report of the Plasma Science and Innovation Center (PSI-Center) covering March 2014 through February 2017. The Center has accomplished a great deal during this period. The PSI-Center is organized into four groups: Edge and Dynamic Neutrals; Transport and Kinetic Effects; Equilibrium, Stability, and Kinetic Effects in 3D Topologies; and Interface for Validation. Each group has made good progress and the results from each group are given in detail.

Asymmetric reduction of ketones and β-keto esters by (S)-1-phenylethanol dehydrogenase from denitrifying bacterium Aromatoleum aromaticum.

PubMed

Dudzik, A; Snoch, W; Borowiecki, P; Opalinska-Piskorz, J; Witko, M; Heider, J; Szaleniec, M

2015-06-01

Enzyme-catalyzed enantioselective reductions of ketones and keto esters have become popular for the production of homochiral building blocks which are valuable synthons for the preparation of biologically active compounds at industrial scale. Among many kinds of biocatalysts, dehydrogenases/reductases from various microorganisms have been used to prepare optically pure enantiomers from carbonyl compounds. (S)-1-phenylethanol dehydrogenase (PEDH) was found in the denitrifying bacterium Aromatoleum aromaticum (strain EbN1) and belongs to the short-chain dehydrogenase/reductase family. It catalyzes the stereospecific oxidation of (S)-1-phenylethanol to acetophenone during anaerobic ethylbenzene mineralization, but also the reverse reaction, i.e., NADH-dependent enantioselective reduction of acetophenone to (S)-1-phenylethanol. In this work, we present the application of PEDH for asymmetric reduction of 42 prochiral ketones and 11 β-keto esters to enantiopure secondary alcohols. The high enantioselectivity of the reaction is explained by docking experiments and analysis of the interaction and binding energies of the theoretical enzyme-substrate complexes leading to the respective (S)- or (R)-alcohols. The conversions were carried out in a batch reactor using Escherichia coli cells with heterologously produced PEDH as whole-cell catalysts and isopropanol as reaction solvent and cosubstrate for NADH recovery. Ketones were converted to the respective secondary alcohols with excellent enantiomeric excesses and high productivities. Moreover, the progress of product formation was studied for nine para-substituted acetophenone derivatives and described by neural network models, which allow to predict reactor behavior and provides insight on enzyme reactivity. Finally, equilibrium constants for conversion of these substrates were derived from the progress curves of the reactions. The obtained values matched very well with theoretical predictions.

Ebselen alters mitochondrial physiology and reduces viability of rat hippocampal astrocytes.

PubMed

Santofimia-Castaño, Patricia; Salido, Ginés M; González, Antonio

2013-04-01

The seleno-organic compound and radical scavenger ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) have been extensively employed as an anti-inflammatory and neuroprotective compound. However, its glutathione peroxidase activity at the expense of cellular thiols groups could underlie certain deleterious actions of the compound on cell physiology. In this study, we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular viability, the intracellular free-Ca(2+) concentration ([Ca(2+)]c), the mitochondrial free-Ca(2+) concentration ([Ca(2+)]m), and mitochondrial membrane potential (ψm) were analyzed. The caspase-3 activity was also assayed. Our results show that cell viability was reduced by treatment of cells with ebselen, depending on the concentration employed. In the presence of ebselen, we observed an initial transient increase in [Ca(2+)]c that was then followed by a progressive increase to an elevated plateau. We also observed a transient increase in [Ca(2+)]m in the presence of ebselen that returned toward a value over the prestimulation level. The compound induced depolarization of ψm and altered the permeability of the mitochondrial membrane. Additionally, a disruption of the mitochondrial network was observed. Finally, we did not detect changes in caspase-3 activation in response to ebselen treatment. Collectively, these data support the likelihood of ebselen, depending on the concentration employed, reduces viability of rat hippocampal astrocytes via its action on the mitochondrial activity. These may be early effects that do not involve caspase-3 activation. We conclude that, depending on the concentration used, ebselen might exert deleterious actions on astrocyte physiology that could compromise cell function.

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

Effect of volatile compounds on excimer laser power delivery.

PubMed

Van Horn, Stewart D; Hovanesian, John A; Maloney, Robert K

2002-01-01

To determine whether vapors from perfume, hairspray, oil-based paint, or water-based paint affect excimer laser beam power delivery at the corneal surface. We measured the power delivery of an Apex Plus laser before, during, and after exposure to vapors from the following volatile compounds: three types of perfume, hair spray, an oil-based paint, and a water-based paint. A digital calorimeter was used to measure the steady-state beam power of the laser during laser discharge at the corneal plane. Multiple trials were run with each compound, and the change in laser energy over time was examined to determine if any of the compounds caused degradation of the laser optics. The presence of a volatile compound in the room caused no change in mean laser energy in comparison to before and after the compound was present. However, perfumes caused a progressive decline in laser beam power throughout the trials. Controlling for this progressive decline, there was no significant difference from perfume to perfume. None of the compounds tested caused a decline in laser beam power while present in the room. However, the presence of any perfume caused a deterioration in beam power over time, suggesting a degradation of the laser optics for all perfumes. Laser centers should consider advising their patients and staff to not wear perfumes in the laser suite.

Imbricatolic acid from Juniperus communis L. prevents cell cycle progression in CaLu-6 cells.

PubMed

De Marino, Simona; Cattaneo, Fabio; Festa, Carmen; Zollo, Franco; Iaccio, Annalisa; Ammendola, Rosario; Incollingo, Filomena; Iorizzi, Maria

2011-11-01

Imbricatolic acid was isolated from the methanolic extract of the fresh ripe berries of Juniperus communis (Cupressaceae) together with sixteen known compounds and a new dihydrobenzofuran lignan glycoside named juniperoside A. Their structures were determined by spectroscopic methods and by comparison with the spectral data reported in literature. Imbricatolic acid was evaluated for its ability to prevent cell cycle progression in p53-null CaLu-6 cells. This compound induces the upregulation of cyclin-dependent kinase inhibitors and their accumulation in the G1 phase of the cell cycle, as well as the degradation of cyclins A, D1, and E1. Furthermore, no significant imbricatolic acid-induced apoptosis was observed. Therefore, this plant-derived compound may play a role in the control of cell cycle. © Georg Thieme Verlag KG Stuttgart · New York.

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

Chemopreventive potential of natural compounds in head and neck cancer.

PubMed

Rahman, Mohammad Aminur; Amin, A R M Ruhul; Shin, Dong M

2010-01-01

Head and neck squamous cell carcinoma (HNSCC) is one of the most fatal cancers worldwide. Despite advances in the management of HNSCC, the overall survival for patients has not improved significantly due to advanced stages at diagnosis, high recurrence rate after surgical removal, and second primary tumor development, which underscore the importance of novel strategies for cancer prevention. Cancer chemoprevention, the use of natural or synthetic compounds to prevent, arrest, or reverse the process of carcinogenesis at its earliest stages, aims to reverse premalignancies and prevent second primary tumors. Genomics and proteomics information including initial mutation, cancer promotion, progression, and susceptibility has brought molecularly targeted therapies for drug development. The development of preventive approaches using specific natural or synthetic compounds, or both, requires a depth of understanding of the cross-talk between cancer signaling pathways and networks to retain or enhance chemopreventive activity while reducing known toxic effects. Many natural dietary compounds have been identified with multiple molecular targets, effective in the prevention and treatment of cancer. This review describes recent advances in the understanding of the complex signaling networks driving cancer progression and of molecularly targeted natural compounds under preclinical and clinical investigation.

Vitamin D compounds inhibit cancer stem-like cells and induce differentiation in triple negative breast cancer.

PubMed

Shan, Naing Lin; Wahler, Joseph; Lee, Hong Jin; Bak, Min Ji; Gupta, Soumyasri Das; Maehr, Hubert; Suh, Nanjoo

2017-10-01

Triple-negative breast cancer is one of the least responsive breast cancer subtypes to available targeted therapies due to the absence of hormonal receptors, aggressive phenotypes, and the high rate of relapse. Early breast cancer prevention may therefore play an important role in delaying the progression of triple-negative breast cancer. Cancer stem cells are a subset of cancer cells that are thought to be responsible for tumor progression, treatment resistance, and metastasis. We have previously shown that vitamin D compounds, including a Gemini vitamin D analog BXL0124, suppress progression of ductal carcinoma in situ in vivo and inhibit cancer stem-like cells in MCF10DCIS mammosphere cultures. In the present study, the effects of vitamin D compounds in regulating breast cancer stem-like cells and differentiation in triple-negative breast cancer were assessed. Mammosphere cultures, which enriches for breast cancer cells with stem-like properties, were used to assess the effects of 1α,25(OH) 2 D 3 and BXL0124 on cancer stem cell markers in the triple-negative breast cancer cell line, SUM159. Vitamin D compounds significantly reduced the mammosphere forming efficiency in primary, secondary and tertiary passages of mammospheres compared to control groups. Key markers of cancer stem-like phenotype and pluripotency were analyzed in mammospheres treated with 1α,25(OH) 2 D 3 and BXL0124. As a result, OCT4, CD44 and LAMA5 levels were decreased. The vitamin D compounds also down-regulated the Notch signaling molecules, Notch1, Notch2, Notch3, JAG1, JAG2, HES1 and NFκB, which are involved in breast cancer stem cell maintenance. In addition, the vitamin D compounds up-regulated myoepithelial differentiating markers, cytokeratin 14 and smooth muscle actin, and down-regulated the luminal marker, cytokeratin 18. Cytokeratin 5, a biomarker associated with basal-like breast cancer, was found to be significantly down-regulated by the vitamin D compounds. These results suggest that vitamin D compounds may serve as potential preventive agents to inhibit triple negative breast cancer by regulating cancer stem cells and differentiation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Guaranteed Time Observations Support for Goddard High Resolution Spectrograph (GHRS) on HST

NASA Technical Reports Server (NTRS)

Beaver, Edward

1998-01-01

We assemble this final grant report by combining our previously submitted progress reports with the last year's progress report. Section 2 is the progress report for the June 1, 1991 to Nov. 14, 1995 period. Section 4 is the progress report for the Nov. 14, 1996 to Dec. 31, 1996 period. Section 5 is the progress report for the Nov. 14 to Aug. 31, 1997 period. Section 6 is the new progress report for the Sept. 15, 1997 to Nov. 14, 1998 final period. Section 3 is a summary of our spare detector high voltage transient tests activity in 1992 in support of the renewed safe operation of the GHRS HST D1 detector. Note that we have left the format of each progress report the same as originally sent out. The slight differences in format presentation are thus intended.

Far infrared filters for the Galileo-Jupiter and other missions

NASA Technical Reports Server (NTRS)

Seeley, J. S.; Hunneman, R.; Whatley, A.

1981-01-01

Progress in the development of FIR multilayer interference filters for the net flux radiometer and photopolarizing radiometer to be carried on board the Galileo mission to Jupiter is reported. The multilayer interference technique has been extended to the region above 40 microns by the use of PbTe/II-VI materials in hard-coated combination, with the thickest layers composed of CdSe QWOT at 74 microns and PbTe QWOT. Improvements have also been obtained in filters below 20 microns on the basis of the Chebyshev stack design. A composite filter cutting on steeply at 40 microns has been designed which employs a thin crystal quartz substrate, shorter wavelength absorption in ZnS and As2S3 thin films, and supplementary multilayer interference. Finally, absorptive filters have been developed based on II-VI compounds in multilayer combination with KRS-5 (or 6) on a KRS-5 (or 6) substrate

Understanding of Leaf Development-the Science of Complexity.

PubMed

Malinowski, Robert

2013-06-25

The leaf is the major organ involved in light perception and conversion of solar energy into organic carbon. In order to adapt to different natural habitats, plants have developed a variety of leaf forms, ranging from simple to compound, with various forms of dissection. Due to the enormous cellular complexity of leaves, understanding the mechanisms regulating development of these organs is difficult. In recent years there has been a dramatic increase in the use of technically advanced imaging techniques and computational modeling in studies of leaf development. Additionally, molecular tools for manipulation of morphogenesis were successfully used for in planta verification of developmental models. Results of these interdisciplinary studies show that global growth patterns influencing final leaf form are generated by cooperative action of genetic, biochemical, and biomechanical inputs. This review summarizes recent progress in integrative studies on leaf development and illustrates how intrinsic features of leaves (including their cellular complexity) influence the choice of experimental approach.

Understanding of Leaf Development—the Science of Complexity

PubMed Central

Malinowski, Robert

2013-01-01

The leaf is the major organ involved in light perception and conversion of solar energy into organic carbon. In order to adapt to different natural habitats, plants have developed a variety of leaf forms, ranging from simple to compound, with various forms of dissection. Due to the enormous cellular complexity of leaves, understanding the mechanisms regulating development of these organs is difficult. In recent years there has been a dramatic increase in the use of technically advanced imaging techniques and computational modeling in studies of leaf development. Additionally, molecular tools for manipulation of morphogenesis were successfully used for in planta verification of developmental models. Results of these interdisciplinary studies show that global growth patterns influencing final leaf form are generated by cooperative action of genetic, biochemical, and biomechanical inputs. This review summarizes recent progress in integrative studies on leaf development and illustrates how intrinsic features of leaves (including their cellular complexity) influence the choice of experimental approach. PMID:27137383

Isolated lower brachial plexus (Klumpke) palsy with compound arm presentation: case report.

PubMed

Buchanan, Edward P; Richardson, Randal; Tse, Raymond

2013-08-01

Klumpke palsy has yet to be clearly documented in the newborn, because previous reports lack any description of the obstetrical history, clinical progression, or outcome. Based on a high incidence of breach presentation in the few clinical series that report Klumpke palsy, hyperabduction with arm overhead during delivery has been the presumed mechanism. We report a child with isolated lower brachial plexus palsy and Horner syndrome who presented at birth with a vertex compound arm presentation. Recognition of this condition and details of the clinical progression and outcome are important, because guidelines for management are currently not available. Copyright © 2013. Published by Elsevier Inc.

Comparison of the effects of the antiestrogens EM-800 and tamoxifen on the growth of human breast ZR-75-1 cancer xenografts in nude mice.

PubMed

Couillard, S; Gutman, M; Labrie, C; Bélanger, A; Candas, B; Labrie, F

1998-01-01

Although estrone supplementation in ovariectomized (OVX) nude mice bearing ZR-75-1 xenografts caused a 365% increase in average tumor size during the 4-month treatment period, administration of the antiestrogen EM-800 at the daily oral doses of 50, 150, or 400 microg completely prevented estrogen-stimulated tumor growth. At the same doses of tamoxifen, tumor size was inhibited to 189, 117, and 120% above pretreatment values. However, when EM-800 (150 microg/day) was added to the daily 150- and 400-microg doses of tamoxifen, final tumor size was decreased further to 12 and 38% above pretreatment values, respectively. EM-800 (400 microg daily) administered to estrone-supplemented OVX mice caused complete, partial, and stable responses in 11, 22, and 49% of estrone-stimulated tumors, respectively, whereas 19% (7 of 37) progressed. At the same dose of tamoxifen, the corresponding responses were 3% (complete response), 3% (partial response), and 25% (no change), whereas 69% (22 of 32) of tumors progressed. In the absence of estrone supplementation, tamoxifen (400 microg) alone administered to OVX mice stimulated tumor growth to 161% compared with initial size whereas the same dose of EM-800 reduced tumor size by 55%, a value superimposable to that observed in OVX control animals. The agonistic effect of tamoxifen is thus illustrated by the observation that 73% of tumors progressed when tamoxifen was administered alone to OVX animals whereas no tumor progressed with EM-800. The present data strongly suggest that at least part of the initial lack of response and resistance to tamoxifen during tamoxifen treatment in women is due to the estrogenic activity of this compound, whereas the new antiestrogen EM-800 exerts pure antagonistic action.

GPRC6A regulates prostate cancer progression

PubMed Central

Pi, Min; Quarles, L. Darryl

2011-01-01

BACKGROUND GPRC6A is a nutrient sensing GPCR that is activated in vitro by a variety of ligands, including amino acids, calcium, zinc, osteocalcin (OC) and testosterone. The association between nutritional factors and risk of prostate cancer, the finding of increased expression of OC in prostate cancer cells and the association between GPRC6A and risk of prostate cancer in Japanese men implicates a role of GPRC6A in prostate cancer. METHODS We examined if GPRC6A is expressed in human prostate cancer cell lines and used siRNA-mediated knockdown GPRC6A expression in prostate cancer cells to explore the function of GPRC6A in vitro. To assess the role GPRC6A in prostate cancer progression in vivo we intercrossed Gprc6a−/− mice onto the TRAMP mouse prostate cancer model. RESULTS GPRC6A transcripts were markedly increased in prostate cancer cell lines 22Rv1, PC-3 and LNCaP, compared to the normal prostate RWPE-1 cell line. In addition, a panel of GPRC6A ligands, including calcium, OC, and arginine, exhibited in prostate cancer cell lines a dose-dependent stimulation of ERK activity, cell proliferation, chemotaxis, and prostate specific antigen and Runx 2 gene expression. These responses were inhibited by siRNA-mediated knockdown of GPRC6A. Finally, transfer of Gprc6a deficiency onto a TRAMP mouse model of prostate cancer significantly retarded prostate cancer progression and improved survival of compound Gprc6a−/−/TRAMP mice. CONCLUSIONS GPRC6A is a novel molecular target for regulating prostate growth and cancer progression. Increments in GPRC6A may augment the ability of prostate cancer cells to proliferate in response to dietary and bone derived ligands. PMID:21681779

Transition Metal Compounds Towards Holography

PubMed Central

Dieckmann, Volker; Eicke, Sebastian; Springfeld, Kristin; Imlau, Mirco

2012-01-01

We have successfully proposed the application of transition metal compounds in holographic recording media. Such compounds feature an ultra-fast light-induced linkage isomerization of the transition-metal–ligand bond with switching times in the sub-picosecond regime and lifetimes from microseconds up to hours at room temperature. This article highlights the photofunctionality of two of the most promising transition metal compounds and the photophysical mechanisms that are underlying the hologram recording. We present the latest progress with respect to the key measures of holographic media assembled from transition metal compounds, the molecular embedding in a dielectric matrix and their impressive potential for modern holographic applications. PMID:28817028

The recent progress of isoxazole in medicinal chemistry.

PubMed

Zhu, Jie; Mo, Jun; Lin, Hong-Zhi; Chen, Yao; Sun, Hao-Peng

2018-05-28

Isoxazole compounds exhibit a wide spectrum of targets and broad biological activities. Developing compounds with heterocycle rings has been one of the trends. The integration of isoxazole ring can offer improved physical-chemical properties. Because of the unique profiles, isoxazole ring becomes a popular moiety in compounds design. In this review article, the major focus has been paid to the applications of isoxazole compounds in treating multiple diseases, including anticancer, antimicrobial, anti-inflammatory, etc. Strategies for compounds design for preclinical, clinical, and FDA approved drugs were discussed. Also, the emphasis has been addressed to the future perspectives and trend for the application. Copyright © 2018 Elsevier Ltd. All rights reserved.

Detoxification of Mycotoxins and Other Compounds of Military Interest

DTIC Science & Technology

1987-01-14

h to A conclusion. A newly recognized naturally occurring gILLathione derivative y ltmlguttin)hs enpnae and methods for large scale preparation of...whereas ochers contained as much as 50-70% of the new material. An effort is currently in progress in order to determine the nature of the new compound

Quinazoline derivatives as potential anticancer agents: a patent review (2007 - 2010).

PubMed

Marzaro, Giovanni; Guiotto, Adriano; Chilin, Adriana

2012-03-01

Due to the increase in knowledge about cancer pathways, there is a growing interest in finding novel potential drugs. Quinazoline is one of the most widespread scaffolds amongst bioactive compounds. A number of patents and papers appear in the literature regarding the discovery and development of novel promising quinazoline compounds for cancer chemotherapy. Although there is a progressive decrease in the number of patents filed, there is an increasing number of biochemical targets for quinazoline compounds. This paper provides a comprehensive review of the quinazolines patented in 2007 - 2010 as potential anticancer agents. Information from articles published in international peer-reviewed journals was also included, to give a more exhaustive overview. From about 1995 to 2006, the anticancer quinazolines panorama has been dominated by the 4-anilinoquinazolines as tyrosine kinase inhibitors. The extensive researches conducted in this period could have caused the progressive reduction in the ability to file novel patents as shown in the 2007 - 2010 period. However, the growing knowledge of cancer-related pathways has recently highlighted some novel potential targets for therapy, with quinazolines receiving increasing attention. This is well demonstrated by the number of different targets of the patents considered in this review. The structural heterogeneity in the patented compounds makes it difficult to derive general pharmacophores and make comparisons among claimed compounds. On the other hand, the identification of multi-target compounds seems a reliable goal. Thus, it is reasonable that quinazoline compounds will be studied and developed for multi-target therapies.

ATG4B inhibitors with a benzotropolone core structure block autophagy and augment efficiency of chemotherapy in mice.

PubMed

Kurdi, Ammar; Cleenewerck, Matthias; Vangestel, Christel; Lyssens, Sophie; Declercq, Wim; Timmermans, Jean-Pierre; Stroobants, Sigrid; Augustyns, Koen; De Meyer, Guido R Y; Van Der Veken, Pieter; Martinet, Wim

2017-08-15

Autophagy is a cell survival mechanism hijacked by advanced tumors to endure a rough microenvironment. Late autophagy inhibitors such as (hydroxy)chloroquine have been used clinically to halt tumor progression with modest success. However, given the toxic nature of these compounds and their lack of specificity, novel targets should be considered. We recently identified a benzotropolone derivative that significantly inhibited the essential autophagy protein ATG4B. Therefore, we synthesized and tested additional benzotropolone compounds to identify a promising ATG4B inhibitor that impairs autophagy both in vitro and in vivo. A compound library containing 27 molecules with a benzotropolone backbone was synthesized and screened for inhibition of recombinant ATG4B. Depending on the benzotropolone compound, inhibition of recombinant ATG4B ranged from 3 to 82%. Active compounds were evaluated in cellular assays to confirm inhibition of ATG4B and suppression of autophagy. Seven compounds inhibited processing of the autophagy protein LC3 and autophagosome formation. Compound UAMC-2526 was selected for further in vivo use because of its fair plasma stability. This compound abolished autophagy both in nutrient-deprived GFP-LC3 mice and in CD1 -/- Foxn1nu mice bearing HT29 colorectal tumor xenografts. Moreover, addition of UAMC-2526 to the chemotherapy drug oxaliplatin significantly improved inhibition of tumor growth. Our data indicate that suppression of autophagy via ATG4B inhibition is a feasible strategy to augment existing chemotherapy efficacy and to halt tumor progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Discovery of N-{3-[(ethanimidoylamino)methyl]benzyl}-l-prolinamide dihydrochloride: A new potent and selective inhibitor of the inducible nitric oxide synthase as a promising agent for the therapy of malignant glioma.

PubMed

Maccallini, Cristina; Di Matteo, Mauro; Gallorini, Marialucia; Montagnani, Monica; Graziani, Valentina; Ammazzalorso, Alessandra; Amoia, Pasquale; De Filippis, Barbara; Di Silvestre, Sara; Fantacuzzi, Marialuigia; Giampietro, Letizia; Potenza, Maria A; Re, Nazzareno; Pandolfi, Assunta; Cataldi, Amelia; Amoroso, Rosa

2018-05-25

In mammalian cells, aberrant iNOS induction may have detrimental consequences, and seems to be involved in the proliferation and progression of different tumors, such as malignant gliomas. Therefore, selective inhibition of iNOS could represent a feasible therapeutic strategy to treat these conditions. In this context, we have previously disclosed new acetamidines able to inhibit iNOS with a very high selectivity profile over eNOS or nNOS. Here we report the synthesis of a new series of compounds structurally related to the leading scaffold of N-[(3-aminomethyl)benzyl] acetamidine (1400 W), together with their in vitro activity and selectivity. Compound 39 emerged as the most promising molecule of this series, and it was ex vivo evaluated on isolated and perfused resistance arteries, confirming a high selectivity toward iNOS inhibition. Moreover, C6 rat glioma cell lines biological response to 39 was investigated, and preliminary MTT assay showed a significant decrease in cell metabolic activity of C6 rat glioma cells. Finally, results of a docking study shed light on the binding mode of 39 into NOS catalytic site. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Molecular dynamics in supercooled liquid and glassy states of antibiotics: azithromycin, clarithromycin and roxithromycin studied by dielectric spectroscopy. Advantages given by the amorphous state.

PubMed

Adrjanowicz, K; Zakowiecki, D; Kaminski, K; Hawelek, L; Grzybowska, K; Tarnacka, M; Paluch, M; Cal, K

2012-06-04

Antibiotics are chemical compounds of extremely important medical role. Their history can be traced back more than one hundred years. Despite the passing time and significant progress made in pharmacy and medicine, treatment of many bacterial infections without antibiotics would be completely impossible. This makes them particularly unique substances and explains the unflagging popularity of antibiotics within the medical community. Herein, using dielectric spectroscopy we have studied the molecular mobility in the supercooled liquid and glassy states of three well-known antibiotic agents: azithromycin, clarithromycin and roxithromycin. Dielectric studies revealed a number of relaxation processes of different molecular origin. Besides the primary α-relaxation, observed above the respective glass transition temperatures of antibiotics, two secondary relaxations in the glassy state were identified. Interestingly, the fragility index as well as activation energies of the secondary processes turned out to be practically the same for all three compounds, indicating probably much the same molecular dynamics. Long-term stability of amorphous antibiotics at room temperature was confirmed by X-ray diffraction technique, and calorimetric studies were performed to evaluate the basic thermodynamic parameters. Finally, we have also checked the experimental solubility advantages given by the amorphous form of the examined antibiotics.

Molecular dynamics and crystallization phenomenon of supercooled and glassy DNA and RNA nucleosides: β-adenosine, β-thymidine, and β-uridine

NASA Astrophysics Data System (ADS)

Adrjanowicz, K.; Wojnarowska, Z.; Grzybowska, K.; Hawelek, L.; Kaminski, K.; Paluch, M.; Kasprzycka, A.; Walczak, K.

2011-11-01

Nucleosides are chemical compounds that have an extremely important biological role; they can be found in all types of living organisms. They are crucial components from which DNA and RNA acids are built. In addition, nucleosides are key regulators of many physiological processes. In this paper, the molecular dynamics in the liquid and glassy state of three selected nucleosides, β-adenosine, β-thymidine, and β-uridine, was investigated by means of dielectric spectroscopy. Our results revealed multiple relaxation processes associated with different types of molecular motions. Besides the primary α relaxation, two secondary modes in the glassy states of examined compounds were identified. Crystallization progress monitored by dielectric spectroscopy and x-ray diffraction technique at isostructural relaxation conditions revealed that the examined nucleosides possess completely different tendencies to recrystallize from the liquid as well as the glassy state. We have also made an attempt to predict the time scale of molecular motion below the glass transition temperatures of the respective nucleosides to discuss their potential stability at room temperature over prolonged storage time. Finally, combination of molecular mobility studies with evaluation of thermodynamic parameters from calorimetric measurements allowed us to discuss the fundamental roles of both kinetic and thermodynamic factors in governing the physical stability of the glassy state.

Plasminogen binding inhibitors demonstrate unwanted activities on GABAA and glycine receptors in human iPSC derived neurons.

PubMed

Kristensson, Lisbeth; Lundin, Anders; Gustafsson, David; Fryklund, Jan; Fex, Tomas; Louise, Delsing; Ryberg, Erik

2018-05-11

Plasminogen binding inhibitors (PBIs) reduce the risk of bleeding in hemorrhagic conditions. However, generic PBIs are also associated with an increased risk of seizures, an adverse effect linked to unwanted activities towards inhibitory neuronal receptors. Development of novel PBIs serve to remove compounds with such properties, but progress is limited by a lack of higher throughput methods with human translatability. Herein we apply human induced pluripotent stem cell (hiPSC) derived neurons in combination with dynamic mass redistribution (DMR) technology to demonstrate robust and reproducible modulation of both GABA A and glycine receptors. These cells respond to GABA (EC 50 0.33 ± 0.18 μM), glycine (EC 50 11.0 ± 3.7 μM) and additional ligands in line with previous reports from patch clamp technologies. Additionally, we identify and characterize a competitive antagonistic behavior of the prototype inhibitor and drug tranexamic acid (TXA). Finally, we demonstrate proof of concept for effective counter-screening of lead series compounds towards unwanted GABA A receptor activities. No activity was observed for a previously identified PBI candidate drug, AZD6564, whereas a discontinued analog, AZ13267257, could be characterized as a potent GABA A receptor agonist. Copyright © 2018. Published by Elsevier B.V.

Bidirectional-Compounding Effects of Rumination and Negative Emotion in Predicting Impulsive Behavior: Implications for Emotional Cascades.

PubMed

Selby, Edward A; Kranzler, Amy; Panza, Emily; Fehling, Kara B

2016-04-01

Influenced by chaos theory, the emotional cascade model proposes that rumination and negative emotion may promote each other in a self-amplifying cycle that increases over time. Accordingly, exponential-compounding effects may better describe the relationship between rumination and negative emotion when they occur in impulsive persons, and predict impulsive behavior. Forty-seven community and undergraduate participants who reported frequent engagement in impulsive behaviors monitored their ruminative thoughts and negative emotion multiple times daily for two weeks using digital recording devices. Hypotheses were tested using cross-lagged mixed model analyses. Findings indicated that rumination predicted subsequent elevations in rumination that lasted over extended periods of time. Rumination and negative emotion predicted increased levels of each other at subsequent assessments, and exponential functions for these associations were supported. Results also supported a synergistic effect between rumination and negative emotion, predicting larger elevations in subsequent rumination and negative emotion than when one variable alone was elevated. Finally, there were synergistic effects of rumination and negative emotion in predicting number of impulsive behaviors subsequently reported. These findings are consistent with the emotional cascade model in suggesting that momentary rumination and negative emotion progressively propagate and magnify each other over time in impulsive people, promoting impulsive behavior. © 2014 Wiley Periodicals, Inc.

What Do We Know about the Chemistry of Strawberry Aroma?

PubMed

Ulrich, Detlef; Kecke, Steffen; Olbricht, Klaus

2018-04-04

The strawberry, with its unique aroma, is one of the most popular fruits worldwide. The demand for specific knowledge of metabolism in strawberries is increasing. This knowledge is applicable for genetic studies, plant breeding, resistance research, nutritional science, and the processing industry. The molecular basis of strawberry aroma has been studied for more than 80 years. Thus far, hundreds of volatile organic compounds (VOC) have been identified. The qualitative composition of the strawberry volatilome remains controversial though considerable progress has been made during the past several decades. Between 1997 and 2016, 25 significant analytical studies were published. Qualitative VOC data were harmonized and digitized. In total, 979 VOC were identified, 590 of which were found since 1997. However, 659 VOC (67%) were only listed once (single entries). Interestingly, none of the identified compounds were consistently reported in all of the studies analyzed. The present need of data exchange between "omic" technologies requires high quality and robust metabolic data. Such data are unavailable for the strawberry volatilome thus far. This review discusses the divergence of published data regarding both the biological material and the analytical methods. The VOC extraction method is an essential step that restricts interlaboratory comparability. Finally, standardization of sample preparation and data documentation are suggested to improve consistency for VOC quantification and measurement.

In Vivo and In Vitro Metabolites from the Main Diester and Monoester Diterpenoid Alkaloids in a Traditional Chinese Herb, the Aconitum Species

PubMed Central

Zhang, Min; Peng, Chong-sheng; Li, Xiao-bo

2015-01-01

Diester diterpenoid alkaloids (DDAs), such as aconitine (AC), mesaconitine (MA), and hypaconitine (HA), are both pharmacologically active compounds and toxic ingredients in a traditional Chinese herb, the Aconitum species. Many DDA metabolism studies have been performed to explore mechanisms for reducing toxicity in these compounds and in Aconitum species extracts for safe clinical administration. In this review, we summarize recent progress on the metabolism of toxic AC, MA, and HA and corresponding monoester diterpenoid alkaloids (MDAs) in the gastrointestinal tract and liver in different animal species and humans in vivo and/or in vitro, where these alkaloids are primarily metabolized by cytochrome P450 enzymes, carboxylesterases, and intestinal bacteria, which produces phase I metabolites, ester hydrolysed products, and lipoalkaloids. Furthermore, we classify metabolites detected in the blood and urine, where the aforementioned metabolites are absorbed and excreted. Less toxic MDAs and nontoxic alcohol amines are the primary DDA metabolites detected in the blood. Most other DDAs metabolites produced in the intestine and liver detected in the urine have not been reported in the blood. We propose an explanation for this nonconformity. Finally, taking AC, for instance, we generalize a process of toxicity reduction in the body after oral AC administration for the first time. PMID:25705235

Nitrodifluoraminoterphenyl compounds and processes

DOEpatents

Lerom, M.W.; Peters, H.M.

1975-07-08

This patent relates to the nitrodifluoraminoterphenyl compounds: 3,3''-bis (difluoramino)-2,2'' 4,4', 4'',6,6',6''-octanitro-m-terphenyl (DDONT) and 3,3''-bis(difluoramino)-2,2',2''4,4',4'',6,6',6''-nonanitro-m-terphenyl (DDNONA). Procedures are described wherein diamino precursors of the indicated compounds are prepared and the final compounds are obtained by a fluorination operation. The compounds are highly energetic and suitable for use as explosives and particularly in exploding bridge wire (EBW) detonators. (auth)

Heterogeneous Catalysis of Polyoxometalate Based Organic–Inorganic Hybrids

PubMed Central

Ren, Yuanhang; Wang, Meiyin; Chen, Xueying; Yue, Bin; He, Heyong

2015-01-01

Organic–inorganic hybrid polyoxometalate (POM) compounds are a subset of materials with unique structures and physical/chemical properties. The combination of metal-organic coordination complexes with classical POMs not only provides a powerful way to gain multifarious new compounds but also affords a new method to modify and functionalize POMs. In parallel with the many reports on the synthesis and structure of new hybrid POM compounds, the application of these compounds for heterogeneous catalysis has also attracted considerable attention. The hybrid POM compounds show noteworthy catalytic performance in acid, oxidation, and even in asymmetric catalytic reactions. This review summarizes the design and synthesis of organic–inorganic hybrid POM compounds and particularly highlights their recent progress in heterogeneous catalysis. PMID:28788017

Decontamination Systems Information and Research Program. Quarterly technical progress report, January 1--March 31, 1994

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

Not Available

1994-05-01

West Virginia University (WVU) and the US DOE Morgantown Energy Technology Center (METC) entered into a Cooperative Agreement on August 29, 1992 entitled ``Decontamination Systems Information and Research Programs.`` Stipulated within the Agreement is the requirement that WVU submit to METC a series of Technical Progress Reports on a quarterly basis. This report comprises the first Quarterly Technical Progress Report for Year 2 of the Agreement. This report reflects the progress and/or efforts performed on the sixteen (16) technical projects encompassed by the Year 2 Agreement for the period of January 1 through March 31, 1994. In situ bioremediation ofmore » chlorinated organic solvents; Microbial enrichment for enhancing in-situ biodegradation of hazardous organic wastes; Treatment of volatile organic compounds (VOCs) using biofilters; Drain-enhanced soil flushing (DESF) for organic contaminants removal; Chemical destruction of chlorinated organic compounds; Remediation of hazardous sites with steam reforming; Soil decontamination with a packed flotation column; Use of granular activated carbon columns for the simultaneous removal of organics, heavy metals, and radionuclides; Monolayer and multilayer self-assembled polyion films for gas-phase chemical sensors; Compact mercuric iodide detector technology development; Evaluation of IR and mass spectrometric techniques for on-site monitoring of volatile organic compounds; A systematic database of the state of hazardous waste clean-up technologies; Dust control methods for insitu nuclear and hazardous waste handling; Winfield Lock and Dam remediation; and Socio-economic assessment of alternative environmental restoration technologies.« less

Acrylamide formation in different foods and potential strategies for reduction.

PubMed

Stadler, Richard H

2005-01-01

This paper summarizes the progress made to date on acrylamide research pertaining to analytical methods, mechanisms of formation, and mitigation research in the major food categories. Initial difficulties with the establishment of reliable analytical methods have today in most cases been overcome, but challenges still remain in terms of the needs to develop simple and rapid test methods. Several researchers have identified that the main pathway of formation of acrylamide in foods is linked to the Maillard reaction and in particular the amino acid asparagine. Decarboxylation of the resulting Schiff base is a key step, and the reaction product may either furnish acrylamide directly or via 3-aminopropionamide. An alternative proposal is that the corresponding decarboxylated Amadori compound may release acrylamide by a beta-elimination reaction. Many experimental trials have been conducted in different foods, and a number of possible measures identified to relatively lower the amounts of acrylamide in food. The validity of laboratory trials must, however, be assessed under actual food processing conditions. Some progress in relatively lowering acrylamide in certain food categories has been achieved, but can at this stage be considered marginal. However, any options that are chosen to reduce acrylamide must be technologically feasible and also not negatively impact the quality and safety of the final product.

Polyphenolic Nutrients in Cancer Chemoprevention and Metastasis: Role of the Epithelial-to-Mesenchymal (EMT) Pathway

PubMed Central

Amawi, Haneen; Ashby, Charles R.; Peraman, Ramalingam

2017-01-01

The epithelial-to-mesenchymal transition (EMT) has received significant interest as a novel target in cancer prevention, metastasis, and resistance. The conversion of cells from an epithelial, adhesive state to a mesenchymal, motile state is one of the key events in the development of cancer metastasis. Polyphenols have been reported to be efficacious in the prevention of cancer and reversing cancer progression. Recently, the antimetastatic efficacy of polyphenols has been reported, thereby expanding the potential use of these compounds beyond chemoprevention. Polyphenols may affect EMT pathways, which are involved in cancer metastasis; for example, polyphenols increase the levels of epithelial markers, but downregulate the mesenchymal markers. Polyphenols also alter the level of expression and functionality of important proteins in other signaling pathways that control cellular mesenchymal characteristics. However, the specific proteins that are directly affected by polyphenols in these signaling pathways remain to be elucidated. The aim of this review is to analyze current evidence regarding the role of polyphenols in attenuating EMT-mediated cancer progression and metastasis. We also discuss the role of the most important polyphenol subclasses and members of the polyphenols in reversing metastasis and targeting EMT. Finally, limitations and future directions to improve our understanding in this field are discussed. PMID:28825675

Chemopreventive potential of natural compounds in head and neck cancer

PubMed Central

Rahman, Mohammad Aminur; Amin, A.R.M. Ruhul; Shin, Dong M.

2013-01-01

Head and neck squamous cell carcinoma (HNSCC) is one of the most fatal cancers world-wide. Despite advances in the management of HNSCC, the overall survival for patients has not improved significantly due to advanced stages at diagnosis, high recurrence rate after surgical removal, and second primary tumor development, which together underscore the importance of novel strategies for cancer prevention. Cancer chemoprevention, the use of natural or synthetic compounds to prevent, arrest, or reverse the process of carcinogenesis at its earliest stages, aims to reverse premalignancies and prevent second primary tumors. Genomics and proteomics information including initial mutation, cancer promotion, progression and susceptibility has brought molecularly targeted therapies for drug development. The development of preventive approaches using specific natural or synthetic compounds, or both, requires a depth of understanding of the cross-talk between cancer signaling pathways and networks to retain or enhance chemopreventive activity while reducing known toxic effects. Many natural dietary compounds have been identified as multiple molecular targets, effective in the prevention and treatment of cancer. This review describes recent advances in the understanding of the complex signaling networks driving cancer progression using head and neck cancer as a prototype, and of molecularly targeted natural compounds under preclinical and clinical investigation. PMID:20924973

The Biosynthesis of Unusual Floral Volatiles and Blends Involved in Orchid Pollination by Deception: Current Progress and Future Prospects.

PubMed

Wong, Darren C J; Pichersky, Eran; Peakall, Rod

2017-01-01

Flowers have evolved diverse strategies to attract animal pollinators, with visual and olfactory floral cues often crucial for pollinator attraction. While most plants provide reward (e.g., nectar, pollen) in return for the service of pollination, 1000s of plant species, particularly in the orchid family, offer no apparent reward. Instead, they exploit their often specific pollinators (one or few) by mimicking signals of female insects, food source, and oviposition sites, among others. A full understanding of how these deceptive pollination strategies evolve and persist remains an open question. Nonetheless, there is growing evidence that unique blends that often contain unusual compounds in floral volatile constituents are often employed to secure pollination by deception. Thus, the ability of plants to rapidly evolve new pathways for synthesizing floral volatiles may hold the key to the widespread evolution of deceptive pollination. Yet, until now the biosynthesis of these volatile compounds has been largely neglected. While elucidating the biosynthesis in non-model systems is challenging, nonetheless, these cases may also offer untapped potential for biosynthetic breakthroughs given that some of the compounds can be exclusive or dominant components of the floral scent and production is often tissue-specific. In this perspective article, we first highlight the chemical diversity underpinning some of the more widespread deceptive orchid pollination strategies. Next, we explore the potential metabolic pathways and biosynthetic steps that might be involved. Finally, we offer recommendations to accelerate the discovery of the biochemical pathways in these challenging but intriguing systems.

The Biosynthesis of Unusual Floral Volatiles and Blends Involved in Orchid Pollination by Deception: Current Progress and Future Prospects

PubMed Central

Wong, Darren C. J.; Pichersky, Eran; Peakall, Rod

2017-01-01

Flowers have evolved diverse strategies to attract animal pollinators, with visual and olfactory floral cues often crucial for pollinator attraction. While most plants provide reward (e.g., nectar, pollen) in return for the service of pollination, 1000s of plant species, particularly in the orchid family, offer no apparent reward. Instead, they exploit their often specific pollinators (one or few) by mimicking signals of female insects, food source, and oviposition sites, among others. A full understanding of how these deceptive pollination strategies evolve and persist remains an open question. Nonetheless, there is growing evidence that unique blends that often contain unusual compounds in floral volatile constituents are often employed to secure pollination by deception. Thus, the ability of plants to rapidly evolve new pathways for synthesizing floral volatiles may hold the key to the widespread evolution of deceptive pollination. Yet, until now the biosynthesis of these volatile compounds has been largely neglected. While elucidating the biosynthesis in non-model systems is challenging, nonetheless, these cases may also offer untapped potential for biosynthetic breakthroughs given that some of the compounds can be exclusive or dominant components of the floral scent and production is often tissue-specific. In this perspective article, we first highlight the chemical diversity underpinning some of the more widespread deceptive orchid pollination strategies. Next, we explore the potential metabolic pathways and biosynthetic steps that might be involved. Finally, we offer recommendations to accelerate the discovery of the biochemical pathways in these challenging but intriguing systems. PMID:29181016

The Compound Atwood Machine Problem

ERIC Educational Resources Information Center

Coelho, R. Lopes

2017-01-01

The present paper accounts for progress in physics teaching in the sense that a problem, which has been closed to students for being too difficult, is gained for the high school curriculum. This problem is the compound Atwood machine with three bodies. Its introduction into high school classes is based on a recent study on the weighing of an…

The compound Atwood machine problem

NASA Astrophysics Data System (ADS)

Lopes Coelho, R.

2017-05-01

The present paper accounts for progress in physics teaching in the sense that a problem, which has been closed to students for being too difficult, is gained for the high school curriculum. This problem is the compound Atwood machine with three bodies. Its introduction into high school classes is based on a recent study on the weighing of an Atwood machine.

EphB1 as a Novel Drug Target to Combat Pain and Addiction

DTIC Science & Technology

2016-09-01

goals? Strong progress has been made since we changed directions. We have developed a very robust AlphaScreen chemiluminescent assay that probes the...hit compounds, 22, that reduced the chemiluminescent signal >10% at a concentration of 5 uM compound, with 6 of these compounds reducing over 25% (and...we have developed a very robust chemiluminescent Alpha assay that allows us to measure with a high degree of well- to-well consistency in 384 well

New Horizons in C-F Activation by Main Group Electrophiles

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

Ozerov, Oleg V.

2016-02-13

This technical report describes progress on the DOE sponsored project "New Horizons in C-F Activation by Main Group Electrophiles" during the period of 09/15/2010 – 08/31/2015. The main goal of this project was to develop improved catalysts for conversion of carbon-fluorine bonds in potentially harmful compounds. The approach involved combining of a highly reactive positively charged main-group compound with a highly unreactive negatively charged species (anions) as a way to access potent catalysts for carbon-fluorine bond activation. This report details progress made in improving synthetic pathways to a variety of new anions with improved properties and analysis of their potentialmore » in catalysis.« less

Recent Progress in the Study of Inorganic Nanotubes and Fullerene-Like Structures

NASA Astrophysics Data System (ADS)

Tenne, R.; Seifert, G.

2009-08-01

The synthesis of WS2 inorganic nanotubes (INT) and inorganic fullerene-like (IF) structures in 1992 signified the opening of a fertile and challenging field of scientific endeavor. These structures were the first of a long and ever-expanding series of INT and IF structures. Although initially much of the effort concentrated on the synthesis of INT and IF from compounds with layered structures, recently there has been a surge of efforts to synthesize crystalline and polycrystalline nanotubular structures from compounds with quasi-isotropic structures, like spinels, BaTiO3, SiO2, TiO2, and many others. The present review summarizes some of the progress in this field in recent years. Much of the progress in this field was achieved through strong interaction between theoretical and experimental work. This article has four themes: (a) new synthetic approaches leading to new kinds of IF and INT; (b) study of the molecular structure of such nanoparticles with new tools, such as aberration-corrected transmission electron microscopy (TEM) and high-angle annular dark field (HAADF); (c) recent progress in the investigation of the properties of such nanostructures; and (d) examples of applications for which clear progress has been accomplished, in particular in solid lubrication and high-strength nanocomposites.

A Semi-Supervised Approach for Refining Transcriptional Signatures of Drug Response and Repositioning Predictions

PubMed Central

Iorio, Francesco; Shrestha, Roshan L.; Levin, Nicolas; Boilot, Viviane; Garnett, Mathew J.; Saez-Rodriguez, Julio; Draviam, Viji M.

2015-01-01

We present a novel strategy to identify drug-repositioning opportunities. The starting point of our method is the generation of a signature summarising the consensual transcriptional response of multiple human cell lines to a compound of interest (namely the seed compound). This signature can be derived from data in existing databases, such as the connectivity-map, and it is used at first instance to query a network interlinking all the connectivity-map compounds, based on the similarity of their transcriptional responses. This provides a drug neighbourhood, composed of compounds predicted to share some effects with the seed one. The original signature is then refined by systematically reducing its overlap with the transcriptional responses induced by drugs in this neighbourhood that are known to share a secondary effect with the seed compound. Finally, the drug network is queried again with the resulting refined signatures and the whole process is carried on for a number of iterations. Drugs in the final refined neighbourhood are then predicted to exert the principal mode of action of the seed compound. We illustrate our approach using paclitaxel (a microtubule stabilising agent) as seed compound. Our method predicts that glipizide and splitomicin perturb microtubule function in human cells: a result that could not be obtained through standard signature matching methods. In agreement, we find that glipizide and splitomicin reduce interphase microtubule growth rates and transiently increase the percentage of mitotic cells–consistent with our prediction. Finally, we validated the refined signatures of paclitaxel response by mining a large drug screening dataset, showing that human cancer cell lines whose basal transcriptional profile is anti-correlated to them are significantly more sensitive to paclitaxel and docetaxel. PMID:26452147

78 FR 53029 - Air Quality: Revision to Definition of Volatile Organic Compounds-Exclusion of trans

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

... Air Quality: Revision to Definition of Volatile Organic Compounds--Exclusion of trans 1-chloro-3,3,3.... SUMMARY: The EPA is taking final action to revise the regulatory definition of volatile organic compounds..., June 16, 2010), and as a solvent for metals, electronics, and precision cleaning and in adhesives...

77 FR 76419 - Health and Safety Data Reporting; Addition of Certain Chemicals; Withdrawal of Final Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

... importers) of cadmium or cadmium compounds, including as part of an article, that have been, or are... (including importer) of cadmium or cadmium compounds, including as part of an article, that have been, or are... reporting rule that would have required manufacturers (including importers) of cadmium or cadmium compounds...

Feasibility Study of the Development of a Specialized Computer System of Organic Chemical Signatures of Spectral Data.

ERIC Educational Resources Information Center

Scholtz, R. G.; And Others

This final report of a feasibility study describes the research performed in assessing the requirements for a chemical signature file and search scheme for organic compound identification and information retrieval. The research performed to determined feasibility of identifying an unknown compound involved screening the compound against a file of…

Evaluating the Effects of Flexible Learning about Aseptic Compounding on First-year Students in a Pharmacy Skills Laboratory.

PubMed

Neville, Michael W; Palmer, Russ; Elder, Deborah; Fulford, Michael; Morris, Steve; Sappington, Kellie

2015-08-25

To evaluate how flexible learning via online video review affects the ability and confidence of first-year (P1) pharmacy students to accurately compound aseptic preparations. Customary instructions and assignments for aseptic compounding were provided to students, who were given unlimited access to 5 short review videos in addition to customary instruction. Student self-confidence was assessed online, and faculty members evaluated students' aseptic technique at the conclusion of the semester. No significant difference on final assessment scores was observed between those who viewed videos and those who did not. Student self-confidence scores increased significantly from baseline, but were not significantly higher for those who viewed videos than for those who did not. First-year students performed well on final aseptic compounding assessments, and those who viewed videos had a slight advantage. Student self-confidence improved over the semester regardless of whether or not students accessed review videos.

Influence of iodine on the treatment of spacecraft humidity condensate to produce potable water

NASA Technical Reports Server (NTRS)

Symons, James M.; Muckle, Susan V.

1990-01-01

Several compounds in the ersatz humidity condensate do react with iodine to form iodine-substituted organic compounds (TOI), most notably phenol, acetaldehyde, ethanol, and sodium formate. Iodination of the ersatz humidity condensate produced 3.0 to 3.5 mg/L of TOI within 24 hours. The TOI that was produced by the passage of the ersatz humidity condensate through the first iodinated resin (IR) in the adsorption system was removed by the granular activated carbon that followed. TOI detected in the final effluent was formed by the reaction of the non-adsorbable condensate compounds with the final IR in the treatment series. The activated carbon bed series in the adsorption system performed poorly in its removal of TOC. The rapid breakthrough of TOC was not surprising, as the ersatz humidity condensate contained several highly soluble organic compounds, alcohols and organic acids.

A PHARMACOKINETIC MODEL FOR ESTIMATING EXPOSURE OF AMERICANS TO DIOXIN-LIKE COMPOUNDS IN THE PAST, PRESENT, AND FUTURE

EPA Science Inventory

Empirical evidence suggests that exposure of Americans to dioxin-like compounds was low during the early decades of the 20th century, then increased during the 1940s and 1950s reaching a peak in the 1960s and 1970s, and progressively decreased to lower levels in the 1980s and 199...

Antifungal Compounds against Candida Infections from Traditional Chinese Medicine

PubMed Central

2017-01-01

Infections caused by Candida albicans, often refractory and with high morbidity and mortality, cause a heavy burden on the public health while the current antifungal drugs are limited and are associated with toxicity and resistance. Many plant-derived molecules including compounds isolated from traditional Chinese medicine (TCM) are reported to have antifungal activity through different targets such as cell membrane, cell wall, mitochondria, and virulence factors. Here, we review the recent progress in the anti-Candida compounds from TCM, as well as their antifungal mechanisms. Considering the diverse targets and structures, compounds from TCM might be a potential library for antifungal drug development. PMID:29445739

Antioxidant effect of Morus nigra on Chagas disease progression.

PubMed

Montenote, Michelly Cristina; Wajsman, Vithor Zuccaro; Konno, Yoichi Takaki; Ferreira, Paulo César; Silva, Regildo Márcio Gonçalves; Therezo, Altino Luiz Silva; Silva, Luciana Pereira; Martins, Luciamáre Perinetti Alves

2017-11-06

Considering the widespread popular use of Morus nigra and the amount of scientific information on its antioxidant and anti-inflammatory activity, the effectiveness of this phytotherapeutic compound in the parasitemia progression during the acute phase of Chagas disease and its role in the development of the inflammatory process as well as its effects on the oxidative damage in the chronic phase of infection were evaluated. Thus, 96 male Swiss mice were randomly divided into eight groups, four groups were uninfected controls, and four groups were intraperitoneally infected with 5.0 x 104 blood trypomastigotes forms of T. cruzi QM2 strain. Four batches composed of one uninfected and one infected group were respectively treated with 70% alcohol solution and 25 μL, 50 μL and 75 μL of the phytotherapeutic compound. Levels of antioxidant elements (TBARS, FRAP, GSH and Sulfhydryl groups) were measured in plasma samples. The phytotherapeutic compound's antioxidant activity was measured by polyphenol and total flavonoid quantification, DPPH, NO, and FRAP method. Our results showed that the vehicle influenced some of the results that may have physiological relevance in Chagas disease. However, an important action of M. nigra tincture was observed in the progression of Chagas disease, since our results demonstrated a reduction in parasitemia of treated groups when compared to controls, especially in the group receiving 25 µL. However, in the chronic phase, the 50-µL dosage presented a better activity on some antioxidant defenses and minimized the tissue inflammatory process. Results indicated an important action of M. nigra tincture on the Chagas disease progression.

Progression of trunk imbalance in adolescent idiopathic scoliosis with a thoracolumbar/lumbar curve: is it predictable at the initial visit?

PubMed

Hwang, Chang Ju; Lee, Choon Sung; Lee, Dong-Ho; Cho, Jae Hwan

2017-11-01

OBJECTIVE Progression of trunk imbalance is an important finding during follow-up of patients with adolescent idiopathic scoliosis (AIS). Nevertheless, no factors that predict progression of trunk imbalance have been identified. The purpose of this study was to identify parameters that predict progression of trunk imbalance in cases of AIS with a structural thoracolumbar/lumbar (TL/L) curve. METHODS This study included 105 patients with AIS and a structural TL/L curve who were followed up at an outpatient clinic. Patients with trunk imbalance (trunk shift ≥ 20 mm) at the initial visit were excluded. All patients were followed up for more than 2 years. Patients were divided into the following groups according to progression of trunk imbalance: 1) Group P, trunk shift ≥ 20 mm at the final visit and degree of progression ≥ 10 mm; and 2) Group NP, trunk shift < 20 mm at the final visit or degree of progression < 10 mm. Radiological parameters included Cobb angle, upper end vertebrae and lower end vertebrae (LEV), LEV tilt, disc wedge angle between LEV and LEV+1, trunk shift, apical vertebral translation, and apical vertebral rotation (AVR). Each parameter was compared between groups. Radiological parameters were assessed at every visit using whole-spine standing anteroposterior radiographs. RESULTS Among the 105 patients examined, 13 showed trunk imbalance with progression ≥ 10 mm at the final visit (Group P). Multivariate logistic regression analysis identified a lower Risser grade (p = 0.002) and a greater initial AVR (p = 0.020) as predictors of progressive trunk imbalance. A change in LEV tilt during follow-up was associated with trunk imbalance (p = 0.001). CONCLUSIONS Risser grade and AVR measured at the initial visit may predict progression of trunk imbalance. Surgeons should consider the risk of progressive trunk imbalance if patients show skeletal immaturity and a greater AVR at the initial visit.

Final Technical Progress Report: Development of Low-Cost Suspension Heliostat; December 7, 2011 - December 6, 2012

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

Bender, W.

2013-01-01

Final technical progress report of SunShot Incubator Solaflect Energy. The project succeeded in demonstrating that the Solaflect Suspension Heliostat design is viable for large-scale CSP installations. Canting accuracy is acceptable and is continually improving as Solaflect improves its understanding of this design. Cost reduction initiatives were successful, and there are still many opportunities for further development and further cost reduction.

Investigation of innovative synthesis of biologically active compounds on the basis of newly developed reactions.

PubMed

Honda, Toshio

2012-01-01

Synthesis of biologically active compounds, including natural products and pharmaceutical agents, is an important and interesting research area since the large structural diversity and complexity of bioactive compounds make them an important source of leads and scaffolds in drug discovery and development. Many structurally and also biologically interesting compounds, including marine natural products, have been isolated from nature and have also been prepared on the basis of a computational design for the purpose of developing medicinal chemistry. In order to obtain a wide variety of derivatives of biologically active compounds from the viewpoint of medicinal chemistry, it is essential to establish efficient synthetic procedures for desired targets. Newly developed reactions should also be used for efficient synthesis of desired compounds. Thus, recent progress in the synthesis of biologically active compounds by focusing on the development of new reactions is summarized in this review article.

Curcumin and Apigenin – novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease

PubMed Central

Venigalla, Madhuri; Gyengesi, Erika; Münch, Gerald

2015-01-01

Alzheimer's disease is a progressive neurodegenerative disorder, characterized by deposition of amyloid beta, neurofibrillary tangles, astrogliosis and microgliosis, leading to neuronal dysfunction and loss in the brain. Current treatments for Alzheimer's disease primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for Alzheimer's disease patients. This review will provide an overview of the proven antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of curcumin and apigenin and discuss the potential of these compounds for Alzheimer's disease prevention and treatment. We suggest that these compounds might delay the onset of Alzheimer's disease or slow down its progression, and they should enter clinical trials as soon as possible. PMID:26487830

Assessment and Recommendations of Compounding Education in AACP Member Institutions

PubMed Central

Augustine, Sam; Birnie, Christine; Nagel, Karen; Ray, Dipan; Ruble, James; Scolaro, Kelly; Athay Adams, Jennifer

2012-01-01

In August 2009, the American Association of Colleges of Pharmacy (AACP) Council of Sections established a Task Force to assess the current status of compounding education at its member institutions and to provide recommendations for future direction. The Task Force conducted a survey in late June 2010 of faculty members enrolled in the AACP Pharmaceutics and Pharmacy Practice sections to gain qualitative information of the current state of compounding education. The survey results were then organized around eight curricular topics for which the Task Force members provided interpretations and recommendations. A final report was sent to the AACP Council of Sections on February 15, 2011. This publication provides the information contained in that final report to the professional community. PMID:23049115

Synthesis and Evaluation of the Tumor Cell Growth Inhibitory Potential of New Putative HSP90 Inhibitors.

PubMed

Bizarro, Ana; Sousa, Diana; Lima, Raquel T; Musso, Loana; Cincinelli, Raffaella; Zuco, Vantina; De Cesare, Michelandrea; Dallavalle, Sabrina; Vasconcelos, M Helena

2018-02-13

Heat shock protein 90 (HSP90) is a well-known target for cancer therapy. In a previous work, some of us have reported a series of 3-aryl-naphtho[2,3- d ]isoxazole-4,9-diones as inhibitors of HSP90. In the present work, various compounds with new chromenopyridinone and thiochromenopyridinone scaffolds were synthesized as potential HSP90 inhibitors. Their binding affinity to HSP90 was studied in vitro. Selected compounds ( 5 and 8 ) were further studied in various tumor cell lines regarding their potential to cause cell growth inhibition, alter the cell cycle profile, inhibit proliferation, and induce apoptosis. Their effect on HSP90 client protein levels was also confirmed in two cell lines. Finally, the antitumor activity of compound 8 was studied in A431 squamous cell carcinoma xenografts in nude mice. Our results indicated that treatment with compounds 5 and 8 decreased the proliferation of tumor cell lines and compound 8 induced apoptosis. In addition, these two compounds were able to downregulate selected proteins known as "clients" of HSP90. Finally, treatment of xenografted mice with compound 5 resulted in a considerable dose-dependent inhibition of tumor growth. Our results show that two new compounds with a chromenopyridinone and thiochromenopyridinone scaffold are promising putative HSP90 inhibitors causing tumor cell growth inhibition.

Creating a Holistic Extractables and Leachables (E&L) Program for Biotechnology Products.

PubMed

Li, Kim; Rogers, Gary; Nashed-Samuel, Yasser; Lee, Hans; Mire-Sluis, Anthony; Cherney, Barry; Forster, Ronald; Yeh, Ping; Markovic, Ingrid

2015-01-01

The risk mitigation of extractables and leachables presents significant challenges to regulators and drug manufacturers with respect to the development, as well as the lifecycle management, of drug products. A holistic program is proposed, using a science- and risk-based strategy for testing extractables and leachables from primary containers, drug delivery devices, and single-use systems for the manufacture of biotechnology products. The strategy adopts the principles and concepts from ICH Q9 and ICH Q8(R2). The strategy is phase-appropriate, progressing from extractables testing for material screening/selection/qualification through leachables testing of final products. The strategy is designed primarily to ensure patient safety and product quality of biotechnology products. The holistic program requires robust extraction studies using model solvents, with careful consideration of solvation effect, pH, ionic strength, temperature, and product-contact surface and duration. From a wide variety of process- and product-contact materials, such extraction studies have identified and quantified over 200 organic extractable compounds. The most commonly observed compounds were siloxanes, fatty acid amides, and methacrylates. Toxicology assessments were conducted on these compounds using risk-based decision analysis. Parenteral permitted daily exposure limits were derived, as appropriate, for the majority of these compounds. Analysis of the derived parenteral permitted daily exposure limits helped to establish action thresholds to target high-risk leachables in drug products on stability until expiry. Action thresholds serve to trigger quality investigations to determine potential product impact. The holistic program also evaluates the potential risk for immunogenicity. This approach for primary drug containers and delivery devices is also applicable to single-use systems when justified with a historical knowledge base and understanding of the manufacturing processes of biotechnology products. In the development of a drug product, careful consideration is given to impurities that may originate from manufacturing equipment, process components, and packaging materials. The majority of such impurities are common chemical additives used to improve the physicochemical properties of a wide range of plastic materials. Suppliers and drug manufacturers conduct studies to extract chemical additives from the plastic materials in order to screen and predict those that may leach into a drug product. In this context, the term extractables refers to a profile of extracted compounds observed in studies under harsh conditions. In contrast, the term leachables refers to those impurities that leach from the materials under real-use conditions and may be present in final drug products. The purpose of this article is to present a holistic approach that effectively minimizes the risk of leachables to patient safety and product quality. © PDA, Inc. 2015.

Proceedings of the first international symposium on neutron capture therapy

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

Fairchild, R.G.; Brownell, G.L.

This meeting was arranged jointly by MIT and BNL in order to illuminate progress in the synthesis and targeting of boron compounds and to evaluate and document progress in radiobiological and dosimetric aspects of neutron capture therapy. It is hoped that this meeting will facilitate transfer of information between groups working in these fields, and encourage synergistic collaboration.

Nuclear medicine technology progress report for quarter ending June 30, 1978. ABELLED COMPOUNDS; PATIENTS; POSITRON SOURCES; CARBON 11; ISOMERIC NUCLEI; LABELLED COMPOUNDS; BIOLOGICAL LOCALIZATION; CHEMICAL PREPARATION; ISOMERIC NUCLEI; LABELLED COMPOUNDS; RATS; CHEMICAL PREPARATION; LABELLED COMPOUNDS; RATS; TISSUE DISTRIBUTION

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

Knapp, Jr., F. F.

Progress is reported for the applications of /sup 11/C, /sup 195m/Pt, /sup 75/Se, and /sup 123m/Te. Additional human clinical trials with /sup 11/C-DL-tryptophan and /sup 11/C-l-aminocyclobutane carboxylic acid have been completed. The modified Buecherer-Strecker amino acid synthesis has been used to prepare /sup 11/C-DL-phenylglycine and /sup 11/C-DL-phenylalanine. These two new /sup 11/C-labeled amino acids will be studied as potential tumor localizing agents. Preliminary studies concerning the comparative organ and subcellular distribution of /sup 195m/Pt-labeled cis- and trans- dichlorodiamineplatinum(II) have been completed. The results of in vivo studies have shown the cis isomer to bind to nuclear DNA to a significantlymore » greater extent than the trans isomer. A series of /sup 123m/Te-labeled long-chain fatty acid analogs have been prepared as isosteres of unsaturated fatty acids. Several of these compounds show pronounced heart uptake in rats and may represent a new class of potential myocardial imaging agents. Studies on the preparation and tissue distribution of /sup 75/Se-..beta..-aminoethyl selenosulfate continue.« less

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

Association between volatile sulfur compounds and periodontal disease progression in elderly non-smokers.

PubMed

Makino, Yuka; Yamaga, Takayuki; Yoshihara, Akihiro; Nohno, Kaname; Miyazaki, Hideo

2012-05-01

Periodontal pathogenic microorganisms produce volatile sulfur compounds (VSCs), such as hydrogen sulfide, methyl mercaptan, and dimethyl sulfide. VSCs are toxic to periodontal tissue. Therefore, there is a relationship between periodontitis and the VSC level of mouth air. However, the association between VSC and periodontal disease progression has not been investigated in a longitudinal study. The purpose of this study is to evaluate the association between VSCs in mouth air and periodontal disease progression among elderly dentulous non-smokers. Two hundred forty-one dentulous non-smokers (103 males and 138 females; all 70 years old) had their VSC levels examined with a portable sulfide monitor, and their periodontal status was assessed. Periodontal examinations were performed at baseline and once a year for 3 years to investigate the clinical attachment levels of all teeth. Participants were classified by membership in tertile groups (lowest, middle, and highest) according to the value of baseline VSC measurements. In negative binomial regression analysis, the number of teeth with periodontal disease progression for participants in the highest tertile of VSC measurement was greater (incidence rate ratio of 1.33, P = 0.011) than for the reference group (lowest tertile of VSC measurement) after simultaneously adjusting for sex, number of remaining teeth, and maximum clinical attachment level. VSC measurements were significantly associated with periodontal disease progression in a non-smoking dentulous elderly population. This suggests that VSC measurements are useful for the diagnosis of periodontal disease progression.

15 CFR 990.63 - Discounting and compounding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... NATURAL RESOURCE DAMAGE ASSESSMENTS Restoration Implementation Phase § 990.63 Discounting and compounding. (a) Estimated future restoration costs. When determining estimated future costs of implementing a Final Restoration Plan, trustees must discount such future costs back to the date the demand is...

Immobilization of kojic acid in ZnAl-hydrotalcite like compounds

NASA Astrophysics Data System (ADS)

Ambrogi, Valeria; Perioli, Luana; Nocchetti, Morena; Latterini, Loredana; Pagano, Cinzia; Massetti, Elena; Rossi, Carlo

2012-01-01

Kojic acid (KOJ) is a melanin synthesis inhibitor widely used as skin lightening agent in topical preparations. Unfortunately it is easily susceptible to photo-oxidation, phenomenon responsible for chemical and organoleptic modifications. The aim of this work was the intercalation of KOJ in hydrotalcite-like compounds (HTlc) in order to stabilize KOJ and to reduce its photolability. Hydrotalcite containing Zn and Al (ZnAl-HTlc) was used as host to obtain the final compound ZnAl-HTlc-KOJ. The intercalation was carried out, after many attempts, by ionic exchange mechanism by means of the strong base EtO- in anhydrous ethanol/dimethylsulfoxide (DMSO) mixture as solvent in order to generate KOJ- anions. The final product was characterized by the X-ray powder diffraction (XRPD), FT-IR spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and elemental analysis. The intercalated compound was formulated in a siliconic water free self-emulsifying ointment and the in vitro release profile was evaluated. All samples (intercalation compound and its formulation) were submitted also to spectrophotometric assays in order to evaluate the matrix protective effect towards ultraviolet rays.

Atypical juvenile presentation of GM2 gangliosidosis AB in a patient compound-heterozygote for c.259G > T and c.164C > T mutations in the GM2A gene.

PubMed

Martins, Carla; Brunel-Guitton, Catherine; Lortie, Anne; Gauvin, France; Morales, Carlos R; Mitchell, Grant A; Pshezhetsky, Alexey V

2017-06-01

G M2 -gangliosidosis, AB variant is an extremely rare autosomal recessive inherited disorder caused by mutations in the GM2A gene that encodes G M2 ganglioside activator protein (GM2AP). GM2AP is necessary for solubilisation of G M2 ganglioside in endolysosomes and its presentation to β-hexosaminidase A. Conversely GM2AP deficiency impairs lysosomal catabolism of G M2 ganglioside, leading to its storage in cells and tissues. We describe a 9-year-old child with an unusual juvenile clinical onset of G M2 -gangliosidosis AB. At the age of 3 years he presented with global developmental delay, progressive epilepsy, intellectual disability, axial hypertonia, spasticity, seizures and ataxia, but without the macular cherry-red spots typical for G M2 gangliosidosis. Brain MRI detected a rapid onset of diffuse atrophy, whereas whole exome sequencing showed that the patient is a compound heterozygote for two mutations in GM2A : a novel nonsense mutation, c.259G > T (p.E87X) and a missense mutation c.164C > T (p.P55L) that was recently identified in homozygosity in patients of a Saudi family with a progressive chorea-dementia syndrome. Western blot analysis showed an absence of GM2AP in cultured fibroblasts from the patient, suggesting that both mutations interfere with the synthesis and/or folding of the protein. Finally, impaired catabolism of G M2 ganglioside in the patient's fibroblasts was demonstrated by metabolic labeling with fluorescently labeled G M1 ganglioside and by immunohistochemistry with anti-G M2 and anti-G M3 antibodies. Our observation expands the molecular and clinical spectrum of molecular defects linked to G M2 -gangliosidosis and suggests novel diagnostic approach by whole exome sequencing and perhaps ganglioside analysis in cultured patient's cells.

Research Progress of Natural Product Gentiopicroside - a Secoiridoid Compound.

PubMed

Wu, Shaoping; Ning, Yaoyao; Zhao, Yingyong; Sun, Wenji; Thorimbert, Serge; Dechoux, Luc; Sollogoub, Matthieu; Zhang, Yongmin

2017-01-01

Gentiopicroside is a secoiridoid compound isolated from Gentiana lutea which is called Qin Jiao in Chinese. It is one of the most common herbal medicines used in China. In this article, we review the pharmacological and biological activity (antiviral, anti-inflammatory, analgesia, antihepatotoxic and choleretic), as well as biotransformation of the gentiopicroside. In addition, attempt towards the total synthesis of gentiopicroside is also presented.

Vision Integrating Strategies in Ophthalmology and Neurochemistry (VISION)

DTIC Science & Technology

2012-02-01

23, PPT and DPN (Table 1). The most potent of these compounds, ZYC-3, ZYC-26 and G1 are non- feminizing compared to the inactive compounds; PPT, an...induced cytotoxicity. Although these agents are estrogen analogs, they lack feminizing activity. • Discovered progressive quantitative changes in...Abstract #4619 Nixon ES, Simpkins JW. Neuroprotective effects of non- feminizing estrogen analogues in retinal neurons. 2011 Society for Neuroscience

Creating a dashboard to track progress toward IOM recommendations for the future of nursing.

PubMed

Spetz, Joanne; Bates, Timothy; Chu, Lela; Lin, Jessica; Fishman, Nancy W; Melichar, Lori

2013-01-01

This article explains the process used to identify and develop a set of data used to track national progress toward the recommendations of the Institute of Medicine Committee for the Future of Nursing. The data are presented in a dashboard format to visually summarize information and quickly measure progress. The approach selected by the research team is outlined, the criteria for selecting candidate metrics are detailed, the process for seeking external guidance is described, and the final dashboard measures are presented. Finally, the methods for data collection for each metric are explicated, to guide states and local regions in the collection of their own data.

A Touch-Communication Framework for Drug Delivery Based on a Transient Microbot System.

PubMed

Yifan Chen; Kosmas, Panagiotis; Anwar, Putri Santi; Limin Huang

2015-06-01

Recent progress in bioresorbable radio frequency electronics and engineered bacteria has promised the prospect of realizing a transient microbot (TM) system for therapeutic applications. The inorganic or organic miniature robots will dissolve into the human body after completing the required tasks and cause no side-effect. In this paper, we propose a potential architecture of a TM system for transporting pharmaceutical compounds inside the body, and analyze the system using a micro-to-macro cross-scale communication model. The remote controllability and tangibility of a TM essentially lead to a touch-communication (TouchCom) paradigm. Externally maneuverable and trackable TMs are responsible for the delivery of drug particles (information molecules in the TouchCom context). The loading/injection and unloading of the drug correspond to the transmitting and receiving processes in the TouchCom framework. Subsequently, we investigate simulation tools for the propagation and transient characteristics of TMs in the blood vessels. We also define the propagation delay, path loss, as well as angular and delay spectra of targeting intensity, which are parallel to their counterpart concepts in the conventional wireless channel. Finally, our approach is illustrated with comprehensive simulation studies of targeted drug delivery by using the proposed analytical framework integrating robotics and communications at crossover length scales. The proposed methodology may find important applications in the design and analysis of TM-assisted administration of pharmaceutical compounds.

Protein Kinase-A Inhibition Is Sufficient to Support Human Neural Stem Cells Self-Renewal.

PubMed

Georges, Pauline; Boissart, Claire; Poulet, Aurélie; Peschanski, Marc; Benchoua, Alexandra

2015-12-01

Human pluripotent stem cell-derived neural stem cells offer unprecedented opportunities for producing specific types of neurons for several biomedical applications. However, to achieve it, protocols of production and amplification of human neural stem cells need to be standardized, cost effective, and safe. This means that small molecules should progressively replace the use of media containing cocktails of protein-based growth factors. Here we have conducted a phenotypical screening to identify pathways involved in the regulation of hNSC self-renewal. We analyzed 80 small molecules acting as kinase inhibitors and identified compounds of the 5-isoquinolinesulfonamide family, described as protein kinase A (PKA) and protein kinase G inhibitors, as candidates to support hNSC self-renewal. Investigating the mode of action of these compounds, we found that modulation of PKA activity was central in controlling the choice between self-renewal or terminal neuronal differentiation of hNSC. We finally demonstrated that the pharmacological inhibition of PKA using the small molecule HA1004 was sufficient to support the full derivation, propagation, and long-term maintenance of stable hNSC in absence of any other extrinsic signals. Our results indicated that tuning of PKA activity is a core mechanism regulating hNSC self-renewal and differentiation and delineate the minimal culture media requirement to maintain undifferentiated hNSC in vitro. © 2015 AlphaMed Press.

Methodologies Related to Computational models in View of Developing Anti-Alzheimer Drugs: An Overview.

PubMed

Baheti, Kirtee; Kale, Mayura Ajay

2018-04-17

Since last two decades, there has been more focus on the development strategies related to Anti-Alzheimer's drug research. This may be attributed to the fact that most of the Alzheimer's cases are still mostly unknown except for a few cases, where genetic differences have been identified. With the progress of the disease, the symptoms involve intellectual deterioration, memory impairment, abnormal personality and behavioural patterns, confusion, aggression, mood swings, irritability Current therapies available for this disease give only symptomatic relief and do not focus on manipulations of biololecular processes. Nearly all the therapies to treat Alzheimer's disease, target to change the amyloid cascade which is considered to be an important in AD pathogenesis. New drug regimens are not able to keep pace with the ever-increasing understanding about dementia at molecular level. Looking into these aggravated problems, we though to put forth molecular modeling as a drug discovery approach for developing novel drugs to treat Alzheimer disease. The disease is incurable and it gets worst as it advances and finally causes death. Due to this, the design of drugs to treat this disease has become an utmost priority for research. One of the most important emerging technologies applied for this has been Computer-assisted drug design (CADD). It is a research tool that employs large scale computing strategies in an attempt to develop a model receptor site which can be used for designing of an anti-Alzheimer drug. The various models of amyloid-based calcium channels have been computationally optimized. Docking and De novo evolution are used to design the compounds. These are further subjected to absorption, distribution, metabolism, excretion and toxicity (ADMET) studies to finally bring about active compounds that are able to cross BBB. Many novel compounds have been designed which might be promising ones for the treatment of AD. The present review describes the research carried out on various heterocyclic scaffolds that can serve as lead compounds to design Anti-Alzheimer's drugs in future. The molecular modeling methods can thus become a better alternative for discovery of newer Anti-Alzheimer agents. This methodology is extremely useful to design drugs in minimum time, with enhanced activity keeping balanced ethical considerations. Thus, the researchers are opting for this improved process over the conventional methods hoping to achieve a sure shot way out for the sufferings of people affected by Alzheimer besides other diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Research and development on efficacy of Chinese herbal compound].

PubMed

Liu, Jian-Xun; Ren, Jian-Xun; Lin, Cheng-Ren

2016-03-01

The efficacy not only is summarized by clinical effect of Chinese herbal compound on theory of traditional Chinese medicine, but also is manifested to clinical effect by interaction of many intricate chemical substances. The efficacy of Chinese herbal compound is current research focus in field of traditional Chinese medicine. By currently knowing in different aspects which included the progression in efficacy of Chinese herbal compound, symptomatic efficacy of Chinese herbal compound, the relationship between the efficacy and pharmacologic effect of Chinese herbal compound, the efficacy related pharmacodynamic substance and the evaluation of efficacy, it had been summarized mainly problems and methods in research and development process of the efficacy of Chinese herbal compound in this paper. Paper also elucidated problems that need to pay attention in research of efficacy in order to provide references for clinical and experimental studies of efficacy in Chinese herbal compound, boost research and development level of new traditional Chinese drug and facilitate modernization of traditional Chinese medicines. Copyright© by the Chinese Pharmaceutical Association.

Light Robots: Bridging the Gap between Microrobotics and Photomechanics in Soft Materials.

PubMed

Zeng, Hao; Wasylczyk, Piotr; Wiersma, Diederik S; Priimagi, Arri

2018-06-01

For decades, roboticists have focused their efforts on rigid systems that enable programmable, automated action, and sophisticated control with maximal movement precision and speed. Meanwhile, material scientists have sought compounds and fabrication strategies to devise polymeric actuators that are small, soft, adaptive, and stimuli-responsive. Merging these two fields has given birth to a new class of devices-soft microrobots that, by combining concepts from microrobotics and stimuli-responsive materials research, provide several advantages in a miniature form: external, remotely controllable power supply, adaptive motion, and human-friendly interaction, with device design and action often inspired by biological systems. Herein, recent progress in soft microrobotics is highlighted based on light-responsive liquid-crystal elastomers and polymer networks, focusing on photomobile devices such as walkers, swimmers, and mechanical oscillators, which may ultimately lead to flying microrobots. Finally, self-regulated actuation is proposed as a new pathway toward fully autonomous, intelligent light robots of the future. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wide-angle camera with multichannel architecture using microlenses on a curved surface.

PubMed

Liang, Wei-Lun; Shen, Hui-Kai; Su, Guo-Dung J

2014-06-10

We propose a multichannel imaging system that combines the principles of an insect's compound eye and the human eye. The optical system enables a reduction in track length of the imaging device to achieve miniaturization. The multichannel structure is achieved by a curved microlens array, and a Hypergon lens is used as the main lens to simulate the human eye, achieving large field of view (FOV). With this architecture, each microlens of the array transmits a segment of the overall FOV. The partial images are recorded in separate channels and stitched together to form the final image of the whole FOV by image processing. The design is 2.7 mm thick, with 59 channels; the 100°×80° full FOV is optimized using ZEMAX ray-tracing software on an image plane. The image plane size is 4.53  mm×3.29  mm. Given the recent progress in the fabrication of microlenses, this image system has the potential to be commercialized in the near future.

Therapeutic progress in amyotrophic lateral sclerosis-beginning to learning.

PubMed

Kumar, Vijay; Islam, Asimul; Hassan, Md Imtaiyaz; Ahmad, Faizan

2016-10-04

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle weakness, paralysis and finally death. The proposed mechanisms of ALS include glutamate excitotoxicity, oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and proteasomal dysfunction. Although numerous pathological mechanisms have been explained, ALS remains incurable disease because of failure of clinical trials and lack of any effective therapy. The rapid advancement in genetic discoveries in ALS emphasizes the point that ALS is a multi-subtype syndrome rather than a single disease. This can be argued as one of the single reason why many previous therapeutic drug trials have failed. Efforts to develop novel ALS treatments which target specific pathomechanisms are currently being pursued. Herein, we review the recent discovery and preclinical characterization of neuroprotective compounds and compare their effects on disease onset, duration and survival. Furthermore, the structure-activity relationships of these agents are analyzed with the overall goal of developing a screening strategy for future clinical applications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Isolation and characterisation of microcrystalline cellulose and cellulose nanocrystals from coffee husk and comparative study with rice husk.

PubMed

Collazo-Bigliardi, Sofía; Ortega-Toro, Rodrigo; Chiralt Boix, Amparo

2018-07-01

Cellulosic material from coffee husk has not been previously studied despite being a potential source of reinforcing agents for different applications. This material has been extracted and characterised from coffee husk, in parallel with previously studied rice husk. Samples have been analysed as to their ability to obtain cellulosic fibres and cellulose nanocrystals (CNC) by applying alkali and bleaching treatments and final sulphuric acid hydrolysis. Microstructural changes were analysed after treatments, and the size and aspect ratio of CNCs were determined. Crystallinity and thermal stability of both materials progressed in line with the enrichment in cellulosic compounds. The CNC aspect ratio was higher than 10, which confers good reinforcing properties. These were tested in thermoplastic starch films, whose elastic modulus increased by 186 and 121% when 1 wt% of CNCs from rice and coffee husks, respectively, was incorporated into the matrix. Coffee husk represents an interesting source of cellulosic reinforcing materials. Copyright © 2018 Elsevier Ltd. All rights reserved.

Design of a fragment library that maximally represents available chemical space.

PubMed

Schulz, M N; Landström, J; Bright, K; Hubbard, R E

2011-07-01

Cheminformatics protocols have been developed and assessed that identify a small set of fragments which can represent the compounds in a chemical library for use in fragment-based ligand discovery. Six different methods have been implemented and tested on Input Libraries of compounds from three suppliers. The resulting Fragment Sets have been characterised on the basis of computed physico-chemical properties and their similarity to the Input Libraries. A method that iteratively identifies fragments with the maximum number of similar compounds in the Input Library (Nearest Neighbours) produces the most diverse library. This approach could increase the success of experimental ligand discovery projects, by providing fragments that can be progressed rapidly to larger compounds through access to available similar compounds (known as SAR by Catalog).

Hydraulic Fracturing Fluid Analysis for Regulatory Parameters - A Progress Report

EPA Pesticide Factsheets

This presentation is a progress report on the analysis of Hydraulic Fracturing Fluids for regulatory compounds outlined in the various US EPA methodologies. Fracturing fluids vary significantly in consistency and viscosity prior to fracturing. Due to the nature of the fluids the analytical challenges will have to be addressed. This presentation also outlines the sampling issues associated with the collection of dissolved gas samples.

Automatic indexing of compound words based on mutual information for Korean text retrieval

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

Pan Koo Kim; Yoo Kun Cho

In this paper, we present an automatic indexing technique for compound words suitable to an aggulutinative language, specifically Korean. Firstly, we present the construction conditions to compose compound words as indexing terms. Also we present the decomposition rules applicable to consecutive nouns to extract all contents of text. Finally we propose a measure to estimate the usefulness of a term, mutual information, to calculate the degree of word association of compound words, based on the information theoretic notion. By applying this method, our system has raised the precision rate of compound words from 72% to 87%.

Selected approaches for rational drug design and high throughput screening to identify anti-cancer molecules.

PubMed

Hedvat, Michael; Emdad, Luni; Das, Swadesh K; Kim, Keetae; Dasgupta, Santanu; Thomas, Shibu; Hu, Bin; Zhu, Shan; Dash, Rupesh; Quinn, Bridget A; Oyesanya, Regina A; Kegelman, Timothy P; Sokhi, Upneet K; Sarkar, Siddik; Erdogan, Eda; Menezes, Mitchell E; Bhoopathi, Praveen; Wang, Xiang-Yang; Pomper, Martin G; Wei, Jun; Wu, Bainan; Stebbins, John L; Diaz, Paul W; Reed, John C; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B

2012-11-01

Structure-based modeling combined with rational drug design, and high throughput screening approaches offer significant potential for identifying and developing lead compounds with therapeutic potential. The present review focuses on these two approaches using explicit examples based on specific derivatives of Gossypol generated through rational design and applications of a cancer-specificpromoter derived from Progression Elevated Gene-3. The Gossypol derivative Sabutoclax (BI-97C1) displays potent anti-tumor activity against a diverse spectrum of human tumors. The model of the docked structure of Gossypol bound to Bcl-XL provided a virtual structure-activity-relationship where appropriate modifications were predicted on a rational basis. These structure-based studies led to the isolation of Sabutoclax, an optically pure isomer of Apogossypol displaying superior efficacy and reduced toxicity. These studies illustrate the power of combining structure-based modeling with rational design to predict appropriate derivatives of lead compounds to be empirically tested and evaluated for bioactivity. Another approach to cancer drug discovery utilizes a cancer-specific promoter as readouts of the transformed state. The promoter region of Progression Elevated Gene-3 is such a promoter with cancer-specific activity. The specificity of this promoter has been exploited as a means of constructing cancer terminator viruses that selectively kill cancer cells and as a systemic imaging modality that specifically visualizes in vivo cancer growth with no background from normal tissues. Screening of small molecule inhibitors that suppress the Progression Elevated Gene-3-promoter may provide relevant lead compounds for cancer therapy that can be combined with further structure-based approaches leading to the development of novel compounds for cancer therapy.

Microbial degradation of 2,4-dichlorophenoxyacetic acid: Insight into the enzymes and catabolic genes involved, their regulation and biotechnological implications.

PubMed

Kumar, Ajit; Trefault, Nicole; Olaniran, Ademola Olufolahan

2016-01-01

A considerable progress has been made to understand the mechanisms of biodegradation of 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D biodegradation pathway has been elucidated in many microorganisms including Cupriavidus necator JMP134 (previously known as Wautersia eutropha, Ralstonia eutropha and Alcaligenes eutrophus) and Pseudomonas strains. It generally involves the side chain removal of 2,4-D by α-ketoglutarate-dependent 2,4-D dioxygenase (tfdA) to form 2,4-dichlorophenol (2,4-DCP); hydroxylation of 2,4-DCP by 2,4-DCP hydroxylase (tfdB) to form dichlorocatechol; ortho or meta cleavage of dichlorocatechol by chlorocatechol 1,2-dioxygenase (tfdC) to form 2,4-dichloro-cis,cis-muconate; conversion of 2,4-dichloro-cis,cis-muconate to 2-chlorodienelactone by chloromuconate cycloisomerase (tfdD); conversion of 2-chlorodienelactone to 2-chloromaleylacetate by chlorodienelactone hydrolase (tfdE) and, finally, conversion of 2-chloromaleylacetate to 3-oxoadepate via maleylacetate by chloromaleylacetate reductase and maleylacetate reductase (tfdF), respectively, which is funnelled to the tricarboxylic acid cycle. The latest review on microbial breakdown of 2,4-D, other halogenated aromatic pesticides, and related compounds was compiled by Haggblom, however, a considerable progress has been made in this area of research since then. Thus, this review focuses on the recent advancement on 2,4-D biodegradation, the enzymes, and genes involved and their biotechlogical implications.

Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration

PubMed Central

Mardones, Rodrigo; Jofré, Claudio M.; Minguell, José J.

2015-01-01

Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes. Latterly, an improved alternative for the above reparative strategy involved the infusion of mesenchymal stem cells (MSC), which in addition to a self-renewal capacity exhibit a differentiation potential to chondrocytes, as well as a capability to produce a vast array of growth factors, cytokines and extracellular matrix compounds involved in cartilage development. In addition to the above and foremost reparative options up till now in use, other therapeutic options have been developed, comprising the design of biomaterial substrates (scaffolds) capable of sustaining MSC attachment, proliferation and differentiation. The implantation of these engineered platforms, closely to the site of cartilage damage, may well facilitate the initiation of an ‘in situ’ cartilage reparation process. In this mini-review, we examined the timely and conceptual development of several cell-based methods, designed to repair/regenerate a damaged cartilage. In addition to the above described cartilage reparative options, other therapeutic alternatives still in progress are portrayed. PMID:26019754

Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration.

PubMed

Mardones, Rodrigo; Jofré, Claudio M; Minguell, José J

2015-05-01

Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes. Latterly, an improved alternative for the above reparative strategy involved the infusion of mesenchymal stem cells (MSC), which in addition to a self-renewal capacity exhibit a differentiation potential to chondrocytes, as well as a capability to produce a vast array of growth factors, cytokines and extracellular matrix compounds involved in cartilage development. In addition to the above and foremost reparative options up till now in use, other therapeutic options have been developed, comprising the design of biomaterial substrates (scaffolds) capable of sustaining MSC attachment, proliferation and differentiation. The implantation of these engineered platforms, closely to the site of cartilage damage, may well facilitate the initiation of an 'in situ' cartilage reparation process. In this mini-review, we examined the timely and conceptual development of several cell-based methods, designed to repair/regenerate a damaged cartilage. In addition to the above described cartilage reparative options, other therapeutic alternatives still in progress are portrayed.

Progress of research in treatment of hyperlipidemia by monomer or compound recipe of Chinese herbal medicine.

PubMed

Dou, Xiao-bing; Wo, Xing-de; Fan, Chun-lei

2008-03-01

Hyperlipidemia (HLP) is the No.1 risk factor for patients with atherosclerosis (AS) and is directly related to the occurrence of coronary artery disease (CAD) and cerebrovascular disease. Therefore, prevention and treatment of AS is of great importance and of practical significance in controlling the incidence and mortality of CAD. With its peculiar syndrome-dependent therapy, traditional Chinese medicine (TCM) has accumulated abundant practical experiences in this field and good clinical effects have been achieved. Chinese herbal medicine, with its particularly unique advantages and high potentials yet to be tapped, displays its huge strength in HLP prevention and treatment. The progress of studies concerning prevention and treatment of HLP by Chinese herbal medicines, in the form of monomers or compound recipes, is reviewed in this paper.

Recent progress in the synthesis of thiazolo[3,2-a]pyrimidine compounds

NASA Astrophysics Data System (ADS)

Wu, F. Y.; Luo, Y.; Hu, C. B.

2018-01-01

In this paper, the progress in the synthesis of thiazole[3,2-a]pyrimidine compounds in the field of medicine and pesticide were reviewed. The main synthetic routes include: (i) synthesis of thiazolo[3,2-a]pyrimidines, spiro thiazolo[3,2-a]pyrimidines and pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidines by multicomponent reactions (MCRs). (ii) synthesis of thiazolo[3,2-a]pyrimidines by condensation of pyrimidine-2-thiones, which were obtained by Biginelli reaction between aromatic aldehydes and thiourea, with substituted 2-bromo-1-phenylethanone or chloroacetic acid. (iii) synthesis of pyridothieno-fused thiazolo[3,2-a]pyrimidinones via Pictet-Spengler reaction. (iv) synthesis of pyrido[4,3-d]thiazolo[3,2-a]pyrimidine by reacting 2-aminothiazole with the α, β-unsaturated ketones.

CYP2C19 progress curve analysis and mechanism-based inactivation by three methylenedioxyphenyl compounds.

PubMed

Salminen, Kaisa A; Meyer, Achim; Imming, Peter; Raunio, Hannu

2011-12-01

Several in vitro criteria were used to assess whether three methylenedioxyphenyl (MDP) compounds, the isoquinoline alkaloids bulbocapnine, canadine, and protopine, are mechanism-based inactivators of CYP2C19. The recently reported fluorometric CYP2C19 progress curve analysis approach was applied first to determine whether these alkaloids demonstrate time-dependent inhibition. In this experiment, bulbocapnine, canadine, and protopine displayed time dependence and saturation in their inactivation kinetics with K(I) and k(inact) values of 72.4 ± 14.7 μM and 0.38 ± 0.036 min(-1), 2.1 ± 0.63 μM and 0.18 ± 0.015 min(-1), and 7.1 ± 2.3 μM and 0.24 ± 0.021 min(-1), respectively. Additional studies were performed to determine whether other specific criteria for mechanism-based inactivation were fulfilled: NADPH dependence, irreversibility, and involvement of a catalytic step in the enzyme inactivation. CYP2C19 activity was not significantly restored by dialysis when it had been inactivated by the alkaloids in the presence of a NADPH-regenerating system, and a metabolic-intermediate complex-associated increase in absorbance at approximately 455 nm was observed. In conclusion, the CYP2C19 progress curve analysis method revealed time-dependent inhibition by these alkaloids, and additional experiments confirmed its quasi-irreversible nature. This study revealed that the CYP2C19 progress curve analysis method is useful for identifying novel mechanism-based inactivators and yields a wealth of information in one run. The alkaloids bulbocapnine, canadine, and protopine, present in herbal medicines, are new mechanism-based inactivators and the first MDP compounds exhibiting quasi-irreversible inactivation of CYP2C19.

Analysis of Protein-Phenolic Compound Modifications Using Electrochemistry Coupled to Mass Spectrometry.

PubMed

Kallinich, Constanze; Schefer, Simone; Rohn, Sascha

2018-01-29

In the last decade, electrochemical oxidation coupled with mass spectrometry has been successfully used for the analysis of metabolic studies. The application focused in this study was to investigate the redox potential of different phenolic compounds such as the very prominent chlorogenic acid. Further, EC/ESI-MS was used as preparation technique for analyzing adduct formation between electrochemically oxidized phenolic compounds and food proteins, e.g., alpha-lactalbumin or peptides derived from a tryptic digestion. In the first step of this approach, two reactant solutions are combined and mixed: one contains the solution of the digested protein, and the other contains the phenolic compound of interest, which was, prior to the mixing process, electrochemically transformed to several oxidation products using a boron-doped diamond working electrode. As a result, a Michael-type addition led to covalent binding of the activated phenolic compounds to reactive protein/peptide side chains. In a follow-up approach, the reaction mix was further separated chromatographically and finally detected using ESI-HRMS. Compound-specific, electrochemical oxidation of phenolic acids was performed successfully, and various oxidation and reaction products with proteins/peptides were observed. Further optimization of the reaction (conditions) is required, as well as structural elucidation concerning the final adducts, which can be phenolic compound oligomers, but even more interestingly, quite complex mixtures of proteins and oxidation products.

40 CFR 60.665 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI... level or reading indicated by the organics monitoring device at the outlet of the absorber, condenser... the final recovery device in a recovery system, and where an organic compound monitoring device is not...

40 CFR 60.665 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI... level or reading indicated by the organics monitoring device at the outlet of the absorber, condenser... the final recovery device in a recovery system, and where an organic compound monitoring device is not...

2,3,3,3-tetrafluoropropene No Longer Regulated as a Volatile Organic Compound

EPA Pesticide Factsheets

The Environmental Protection Agency has issued a final rule that identified 2,3,3,3-tetrafluoropropene (also known as HFO-1234yf) as a chemical compound that will no longer be regulated as a VOC under the Clean Air Act.

Evaluating the Effects of Flexible Learning about Aseptic Compounding on First-year Students in a Pharmacy Skills Laboratory

PubMed Central

Palmer, Russ; Elder, Deborah; Fulford, Michael; Morris, Steve; Sappington, Kellie

2015-01-01

Objective. To evaluate how flexible learning via online video review affects the ability and confidence of first-year (P1) pharmacy students to accurately compound aseptic preparations. Design. Customary instructions and assignments for aseptic compounding were provided to students, who were given unlimited access to 5 short review videos in addition to customary instruction. Student self-confidence was assessed online, and faculty members evaluated students’ aseptic technique at the conclusion of the semester. Assessment. No significant difference on final assessment scores was observed between those who viewed videos and those who did not. Student self-confidence scores increased significantly from baseline, but were not significantly higher for those who viewed videos than for those who did not. Conclusion. First-year students performed well on final aseptic compounding assessments, and those who viewed videos had a slight advantage. Student self-confidence improved over the semester regardless of whether or not students accessed review videos. PMID:26430278

Influence of pre-cure freezing on the profile of volatile compounds during the processing of Iberian hams.

PubMed

Pérez-Palacios, Trinidad; Ruiz, Jorge; Martín, Diana; Grau, Raúl; Antequera, Teresa

2010-04-15

This work was designed to study the effect of pre-cure freezing of raw thighs from Iberian pigs on the profile of volatile compounds during the processing of hams. Generation of volatile compounds during Iberian ham processing was similar in both pre-cure frozen and refrigerated hams, the main differences being at the final stage. The levels of 2-methylbutanal, 2-methyl-1-butanol, 2,3-butanediol and 2-heptanol were significantly higher in dry-cured hams that were pre-cure frozen than in refrigerated ones, whereas the content of most detected esters was statistically lower in pre-cure frozen than in refrigerated hams. The effect of pre-cure freezing of Iberian ham on the profile of volatile compounds during ripening was not remarkable. Few differences were found in the final product, which would not greatly modify the aroma and flavour features of the dry-cured hams. (c) 2010 Society of Chemical Industry.

20 CFR 437.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Final request for payment (SF-270) (if applicable). (iv) Invention disclosure (if applicable). (v... are not limited to: (i) Final performance or progress report. (ii) Financial Status Report (SF 269) or...

Heteronuclear Metal Cluster Compounds Synthesis and Reactivity

DTIC Science & Technology

1990-08-10

important role in the formation of complexes with heteronuclear metal - metal bonds. Since this is our Final Report recent results are reported and...DTe FL’ Copy AFOSR-86-0125 Lfl X’ HETERONUCLEAR METAL CLUSTER COMPOUNDS00 SYNTHESIS AND REACTIVITY F. Gordon A. Stone, IDepartment of Inorganic...Security Classification) HETERONUCLEAR METAL CLUSTER COMPOUNDS: SYNTHESIS AND REACTIVITY 12. PERSONAL AUTHOR(S) F. GORDON A. STONE 13a. TYPE OF REPORT

Chemical Preparation Laboratory for IND Candidate Compounds

DTIC Science & Technology

1989-01-31

were prepared in strict compliance with "Current Good Manufacturing Procedures" (CGMP) guidelines. All inter- mediates and final products unreported...TO U.S. ARMY MEDICAL RESARCH INSTITUTE OF INFECTIOUS DISEASES (USANRIID) JANUARY 17. 1938 TO JANUARY 16. 1989 Production N.Compound Amount Control No...RESARCH INSTITUTE OF INFECTIOUS DISEASES (USAMRIID) JANUARY 17. 1988 TO JANUARY 16. 1989. Continued Production No. Compound Amount Control No. AVS 206 l-$-D

Effect of the type of oil on the evolution of volatile compounds of taralli during storage.

PubMed

Giarnetti, Mariagrazia; Caponio, Francesco; Paradiso, Vito M; Summo, Carmine; Gomes, Tommaso

2012-03-01

Baking process leads to a huge quantity of newly formed volatile compounds, which play a major role in developing the flavor of the final product. The aim of this work was to investigate on the evolution of the volatile profile of taralli as a function of both the kind of oil used in the dough and the storage time. The volatile compounds from the taralli were extracted by headspace solid-phase microextraction and analyzed by gas-chromatography/mass spectrometry (GC/MS). Forty-four volatile compounds were identified in taralli, most of which produced by thermically induced reactions occurring during baking process, such as volatiles deriving from Maillard reaction and/or sugar degradation and lipid oxidation. The results obtained demonstrated the essential role played by the type of oil on the formation and on the release of volatile compounds. The volatile compounds significantly increased during storage and their individual levels were in most cases significantly lower in taralli made with extra virgin olive oil than in those made with refined oils. Finally, the taralli made with extra virgin olive oil, compared with those prepared with other vegetable oils, showed to be more resistant to oxidation, probably due to the presence of natural antioxidants. © 2012 Institute of Food Technologists®

Conversion of Azides into Diazo Compounds in Water

PubMed Central

Chou, Ho-Hsuan; Raines, Ronald T.

2013-01-01

Diazo compounds are in widespread use in synthetic organic chemistry, but have untapped potential in chemical biology. We report on the design and optimization of a phosphinoester that mediates the efficient conversion of azides into diazo compounds in phosphate buffer at neutral pH and room temperature. High yields are maintained in the presence of common nucleophilic or electrophilic functional groups, and reaction progress can be monitored by colorimetry. As azido groups are easy to install and maintain in biopolymers or their ligands, this new mode of azide reactivity could have substantial utility in chemical biology. PMID:24053717

Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer’s disease spectrum

PubMed Central

Lowe, Val J.; Graff-Radford, Neill R.; Liesinger, Amanda M.; Cannon, Ashley; Przybelski, Scott A.; Rawal, Bhupendra; Parisi, Joseph E.; Petersen, Ronald C.; Kantarci, Kejal; Ross, Owen A.; Duara, Ranjan; Knopman, David S.; Jack, Clifford R.; Dickson, Dennis W.

2015-01-01

Thal amyloid phase, which describes the pattern of progressive amyloid-β plaque deposition in Alzheimer’s disease, was incorporated into the latest National Institute of Ageing – Alzheimer’s Association neuropathologic assessment guidelines. Amyloid biomarkers (positron emission tomography and cerebrospinal fluid) were included in clinical diagnostic guidelines for Alzheimer’s disease dementia published by the National Institute of Ageing – Alzheimer’s Association and the International Work group. Our first goal was to evaluate the correspondence of Thal amyloid phase to Braak tangle stage and ante-mortem clinical characteristics in a large autopsy cohort. Second, we examined the relevance of Thal amyloid phase in a prospectively-followed autopsied cohort who underwent ante-mortem 11C-Pittsburgh compound B imaging; using the large autopsy cohort to broaden our perspective of 11C-Pittsburgh compound B results. The Mayo Clinic Jacksonville Brain Bank case series (n = 3618) was selected regardless of ante-mortem clinical diagnosis and neuropathologic co-morbidities, and all assigned Thal amyloid phase and Braak tangle stage using thioflavin-S fluorescent microscopy. 11C-Pittsburgh compound B studies from Mayo Clinic Rochester were available for 35 participants scanned within 2 years of death. Cortical 11C-Pittsburgh compound B values were calculated as a standard uptake value ratio normalized to cerebellum grey/white matter. In the high likelihood Alzheimer’s disease brain bank cohort (n = 1375), cases with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE-ε4 positive. Regression modelling in these Alzheimer’s disease cases, showed that Braak tangle stage, but not Thal amyloid phase predicted age at onset, disease duration, and final Mini-Mental State Examination score. In contrast, Thal amyloid phase, but not Braak tangle stage or cerebral amyloid angiopathy predicted 11C-Pittsburgh compound B standard uptake value ratio. In the 35 cases with ante-mortem amyloid imaging, a transition between Thal amyloid phases 1 to 2 seemed to correspond to 11C-Pittsburgh compound B standard uptake value ratio of 1.4, which when using our pipeline is the cut-off point for detection of clear amyloid-positivity regardless of clinical diagnosis. Alzheimer’s disease cases who were older and were APOE-ε4 negative tended to have lower amyloid phases. Although Thal amyloid phase predicted clinical characteristics of Alzheimer’s disease patients, the pre-mortem clinical status was driven by Braak tangle stage. Thal amyloid phase correlated best with 11C-Pittsburgh compound B values, but not Braak tangle stage or cerebral amyloid angiopathy. The 11C-Pittsburgh compound B cut-off point value of 1.4 was approximately equivalent to a Thal amyloid phase of 1–2. PMID:25805643

Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms.

PubMed

Royston, Kendra J; Paul, Bidisha; Nozell, Susan; Rajbhandari, Rajani; Tollefsbol, Trygve O

2018-07-01

Little is known about the effects of combinatorial dietary compounds on the regulation of epigenetic mechanisms involved in breast cancer prevention. The human diet consists of a multitude of components, and there is a need to elucidate how certain compounds interact in collaboration. Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyltransferase (DNMT) inhibitor, and sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor found in cruciferous vegetables, are two epigenetic modifying compounds that have only recently been studied in conjunction. The use of DNMT and HDAC inhibitors to reverse the malignant expression of certain genes in breast cancer has shown considerable promise. Previously, we found that SFN + WA synergistically promote breast cancer cell death. Herein, we determined that these compounds inhibit cell cycle progression from S to G2 phase in MDA-MB-231 and MCF-7 breast cancer. Furthermore, we demonstrate that this unique combination of epigenetic modifying compounds down-regulates the levels of Cyclin D1 and CDK4, and pRB; conversely, the levels of E2F mRNA and tumor suppressor p21 are increased independently of p53. We find these events coincide with an increase in unrestricted histone methylation. We propose SFN + WA-induced breast cancer cell death is attributed, in part, to epigenetic modifications that result in the modulated expression of key genes responsible for the regulation of cancer cell senescence. Copyright © 2018 Elsevier Inc. All rights reserved.

Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function.

PubMed

Ferro, Austin; Carbone, Emily; Marzouk, Evan; Siegel, Asher; Nguyen, Donna; Polley, Kailen; Hartman, Jessilyn; Frederick, Kimberley; Ives, Stephen; Lagalwar, Sarita

2017-01-22

Mitochondrial dysfunction plays a significant role in the aging process and in neurodegenerative diseases including several hereditary spinocerebellar ataxias and other movement disorders marked by progressive degeneration of the cerebellum. The goal of this protocol is to assess mitochondrial dysfunction in Spinocerebellar ataxia type 1 (SCA1) and assess the efficacy of pharmacological targeting of metabolic respiration via the water-soluble compound succinic acid to slow disease progression. This approach is applicable to other cerebellar diseases and can be adapted to a host of water-soluble therapies. Ex vivo analysis of mitochondrial respiration is used to detect and quantify disease-related changes in mitochondrial function. With genetic evidence (unpublished data) and proteomic evidence of mitochondrial dysfunction in the SCA1 mouse model, we evaluate the efficacy of treatment with the water-soluble metabolic booster succinic acid by dissolving this compound directly into the home cage drinking water. The ability of the drug to pass the blood brain barrier can be deduced using high performance liquid chromatography (HPLC). The efficacy of these compounds can then be tested using multiple behavioral paradigms including the accelerating rotarod, balance beam test and footprint analysis. Cytoarchitectural integrity of the cerebellum can be assessed using immunofluorescence assays that detect Purkinje cell nuclei and Purkinje cell dendrites and soma. These methods are robust techniques for determining mitochondrial dysfunction and the efficacy of treatment with water-soluble compounds in cerebellar neurodegenerative disease.

45 CFR 1157.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-10-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

43 CFR 12.90 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-10-01

....) (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

49 CFR 18.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-10-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

45 CFR 1183.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-10-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

45 CFR 1174.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-10-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

28 CFR 66.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-07-01

....) (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

21 CFR 1403.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-04-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

22 CFR 135.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-04-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

Seeking new anti-cancer agents from autophagy-regulating natural products.

PubMed

Hua, Fang; Shang, Shuang; Hu, Zhuo-Wei

2017-04-01

Natural products are an important original source of many widely used drugs, including anti-cancer drugs. Early research efforts for seeking anti-cancer therapy from the natural products are mainly focused on the compounds with cytotoxicity capability. The good examples include vinblastine, vincristine, the camptothecin derivatives; topotecan, irinotecan, epipodophyllotoxin derivatives and paclitaxel. In a recent decade, the fundamental progression has been made in the understanding of molecular and cellular mechanisms regarding tumor initiation, metastasis, therapeutic resistance, immune escape, and relapse, which provide a great opportunity for the development of new mechanism-based anticancer drugs, especially drugs against new molecular and cellular targets. Autophagy, a critical cell homeostasis mechanism and promising drug target involved in a verity of human diseases including cancer, can be modulated by many compounds derived from natural products. In this review, we'll give a short introduction of autophagy and discuss the roles of autophagy in the tumorigenesis and progression. And then, we summarize the accumulated evidences to show the anti-tumor effects of several compounds derived from natural products through modulation of autophagy activity.

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intravascular administration set. 880.5440 Section 880.5440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

FINAL REPORT: MEMBRANE-MEDIATED EXTRACTION AND BIODEGRADATION OF VOLATILE ORGANIC COMPOUNDS FROM AIR

EPA Science Inventory

The report describes feasibility tests of a two-step strategy for air pollution control applicable to exhaust air contaminated with volatile organic compounds (VOCs) from painting aircraft. In the first step, the VOC-contaminated air passes over coated, polypropylene, hollow-fibe...

Coal technology program progress report, February 1976

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

None

Final testing of the 20-atm bench-scale system is underway in preparation for experiments with hydrogen. Laboratory-scale testing of a number of inexpensive pure compounds to improve the settling rate of solids in Solvent Refined Coal (SRC) unfiltered oil (UFO), bench-scale testing of the effect of the Tretolite additive on settling, and characterization tests on a new sample of UFO from the PAMCO-SRC process are reported. Experimental engineering support of an in situ gasification process include low-temperature pyrolyses at exceptionally low heating rates (0.3/sup 0/C/min). Highly pyrophoric chars were consistently produced. Aqueous by-products from coal conversion technologies and oil shale retortingmore » have been analyzed directly to determine major organic components. A report is being prepared discussing various aspects of the engineering evaluations of nuclear process heat for coal. A bench-scale test program on thermochemical water splitting for hydrogen production is under consideration. In the coal-fueled MIUS program, preparations for procurement of tubing for the matrix in the fluidized-bed furnace and for fabrication of the furnace continued. Analyses of the AiResearch gas turbine and recuperator under coal-fueled MIUS operating conditions are near completion. Process flow diagrams and heat and material balances were completed for most of the units in the synthoil process. Overall utilities requirements were calculated and the coal preparation flowsheets were finalized. For hydrocarbonization, the flowsheet was revised to include additional coal data. Flowsheets were finalized for the acid gas separation and recycle, and the oil-solids separation. (LTN)« less

In silico optimization of pharmacokinetic properties and receptor binding affinity simultaneously: a 'parallel progression approach to drug design' applied to β-blockers.

PubMed

Advani, Poonam; Joseph, Blessy; Ambre, Premlata; Pissurlenkar, Raghuvir; Khedkar, Vijay; Iyer, Krishna; Gabhe, Satish; Iyer, Radhakrishnan P; Coutinho, Evans

2016-01-01

The present work exploits the potential of in silico approaches for minimizing attrition of leads in the later stages of drug development. We propose a theoretical approach, wherein 'parallel' information is generated to simultaneously optimize the pharmacokinetics (PK) and pharmacodynamics (PD) of lead candidates. β-blockers, though in use for many years, have suboptimal PKs; hence are an ideal test series for the 'parallel progression approach'. This approach utilizes molecular modeling tools viz. hologram quantitative structure activity relationships, homology modeling, docking, predictive metabolism, and toxicity models. Validated models have been developed for PK parameters such as volume of distribution (log Vd) and clearance (log Cl), which together influence the half-life (t1/2) of a drug. Simultaneously, models for PD in terms of inhibition constant pKi have been developed. Thus, PK and PD properties of β-blockers were concurrently analyzed and after iterative cycling, modifications were proposed that lead to compounds with optimized PK and PD. We report some of the resultant re-engineered β-blockers with improved half-lives and pKi values comparable with marketed β-blockers. These were further analyzed by the docking studies to evaluate their binding poses. Finally, metabolic and toxicological assessment of these molecules was done through in silico methods. The strategy proposed herein has potential universal applicability, and can be used in any drug discovery scenario; provided that the data used is consistent in terms of experimental conditions, endpoints, and methods employed. Thus the 'parallel progression approach' helps to simultaneously fine-tune various properties of the drug and would be an invaluable tool during the drug development process.

Pyrrole and Fused Pyrrole Compounds with Bioactivity against Inflammatory Mediators.

PubMed

Said Fatahala, Samar; Hasabelnaby, Sherifa; Goudah, Ayman; Mahmoud, Ghada I; Helmy Abd-El Hameed, Rania

2017-03-17

A new series of pyrrolopyridines and pyrrolopyridopyrimidines have been synthesized from aminocyanopyrroles. The synthesized compounds have been characterized by FTIR, ¹H-NMR and mass spectroscopy. The final compounds have been screened for in vitro pro-inflammatory cytokine inhibitory and in vivo anti-inflammatory activity. The biological results revealed that among all tested compounds some fused pyrroles, namely the pyrrolopyridines 3i and 3l , show promising activity. A docking study of the active synthesized molecules confirmed the biological results and revealed a new binding pose in the COX-2 binding site.

10 CFR 600.250 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

13 CFR 143.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

15 CFR 24.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

14 CFR 1273.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

Flashback phenomenon and residual neurological deficits after the use of "bath salt" 3, 4- methylenedioxypyrovalerone.

PubMed

Mangold, Aaron R; Bravo, Thomas P; Traub, Stephen J; Maher, Steven A; Lipinski, Christopher A

2014-01-01

The use and abuse of designer drugs has been recognized for decades; however there are many derivatives of compounds that make their way into the community. Abuse of compound(s) known on the street as "bath salt" is on the rise. We report the case of a 33-year-old man who complained of "flashbacks" and right arm shaking that followed a night of "bath salt" snorting. The active compound methylenedioxypyrovalerone methamphetamine (MDPV) was confirmed; however, analysis of three different "bath salt" products showed difference in their active components. The patient's symptoms remained stable and he was discharged home after observation in the emergency department with instructions to return for any symptom progression. Practitioners should be aware of the abuse of the compounds and that not all "bath salt" products contain MDPV.

Comparative analysis of machine learning methods in ligand-based virtual screening of large compound libraries.

PubMed

Ma, Xiao H; Jia, Jia; Zhu, Feng; Xue, Ying; Li, Ze R; Chen, Yu Z

2009-05-01

Machine learning methods have been explored as ligand-based virtual screening tools for facilitating drug lead discovery. These methods predict compounds of specific pharmacodynamic, pharmacokinetic or toxicological properties based on their structure-derived structural and physicochemical properties. Increasing attention has been directed at these methods because of their capability in predicting compounds of diverse structures and complex structure-activity relationships without requiring the knowledge of target 3D structure. This article reviews current progresses in using machine learning methods for virtual screening of pharmacodynamically active compounds from large compound libraries, and analyzes and compares the reported performances of machine learning tools with those of structure-based and other ligand-based (such as pharmacophore and clustering) virtual screening methods. The feasibility to improve the performance of machine learning methods in screening large libraries is discussed.

Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention

PubMed Central

2009-01-01

CYP1A1 is one of the main cytochrome P450 enzymes, examined extensively for its capacity to activate compounds with carcinogenic properties. Continuous exposure to inhalation chemicals and environmental carcinogens is thought to increase the level of CYP1A1 expression in extrahepatic tissues, through the aryl hydrocarbon receptor (AhR). Although the latter has long been recognized as a ligand-induced transcription factor, which is responsible for the xenobiotic activating pathway of several phase I and phase II metabolizing enzymes, recent evidence suggests that the AhR is involved in various cell signaling pathways critical to cell cycle regulation and normal homeostasis. Disregulation of these pathways is implicated in tumor progression. In addition, it is becoming increasingly evident that CYP1A1 plays an important role in the detoxication of environmental carcinogens, as well as in the metabolic activation of dietary compounds with cancer preventative activity. Ultimately the contribution of CYP1A1 to cancer progression or prevention may depend on the balance of procarcinogen activation/detoxication and dietary natural product extrahepatic metabolism. PMID:19531241

Statistical research on the bioactivity of new marine natural products discovered during the 28 years from 1985 to 2012.

PubMed

Hu, Yiwen; Chen, Jiahui; Hu, Guping; Yu, Jianchen; Zhu, Xun; Lin, Yongcheng; Chen, Shengping; Yuan, Jie

2015-01-07

Every year, hundreds of new compounds are discovered from the metabolites of marine organisms. Finding new and useful compounds is one of the crucial drivers for this field of research. Here we describe the statistics of bioactive compounds discovered from marine organisms from 1985 to 2012. This work is based on our database, which contains information on more than 15,000 chemical substances including 4196 bioactive marine natural products. We performed a comprehensive statistical analysis to understand the characteristics of the novel bioactive compounds and detail temporal trends, chemical structures, species distribution, and research progress. We hope this meta-analysis will provide useful information for research into the bioactivity of marine natural products and drug development.

Structure-Based Virtual Screening of Commercially Available Compound Libraries.

PubMed

Kireev, Dmitri

2016-01-01

Virtual screening (VS) is an efficient hit-finding tool. Its distinctive strength is that it allows one to screen compound libraries that are not available in the lab. Moreover, structure-based (SB) VS also enables an understanding of how the hit compounds bind the protein target, thus laying ground work for the rational hit-to-lead progression. SBVS requires a very limited experimental effort and is particularly well suited for academic labs and small biotech companies that, unlike pharmaceutical companies, do not have physical access to quality small-molecule libraries. Here, we describe SBVS of commercial compound libraries for Mer kinase inhibitors. The screening protocol relies on the docking algorithm Glide complemented by a post-docking filter based on structural protein-ligand interaction fingerprints (SPLIF).

A Rotaxane Scaffold for the Construction of Multiporphyrinic Light-Harvesting Devices.

PubMed

Delavaux-Nicot, Béatrice; Ben Aziza, Haifa; Nierengarten, Iwona; Minh Nguyet Trinh, Thi; Meichsner, Eric; Chessé, Matthieu; Holler, Michel; Abidi, Rym; Maisonhaute, Emmanuel; Nierengarten, Jean-François

2018-01-02

A sophisticated photoactive molecular device has been prepared by combining recent concepts for the preparation of multifunctional nanomolecules (click chemistry on multifunctional scaffolds) with supramolecular chemistry (self-assembly to prepare rotaxanes). Specifically, a clickable [2]rotaxane scaffold incorporating a free-base porphyrin stopper has been prepared and functionalized with ten peripheral Zn(II)-porphyrin moieties. Electrochemical investigations of the final compound revealed a peculiar behavior resulting from the intramolecular coordination of the Zn(II) porphyrin moieties to 1,2,3-triazole units. Finally, steady state investigations of the compound combining Zn(II) and free-base porphyrin moieties have shown that this compound is a light-harvesting device capable of channeling the light energy from the peripheral Zn(II)-porphyrin subunits to the core by singlet-singlet energy transfer. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Excellence in the Classroom

ERIC Educational Resources Information Center

Governor's Business Council (Texas), 2006

2006-01-01

Texas has made good progress in education since the school reform movement began in earnest 15 years ago. State test scores are up for all groups of students in all grades in all subjects. On the National Assessment of Educational Progress, Texas is close to the top in student performance in math, and has finally begun to make real progress in…

Preventive and Therapeutic Effects of Chinese Herbal Compounds against Hepatocellular Carcinoma.

PubMed

Hu, Bing; An, Hong-Mei; Wang, Shuang-Shuang; Chen, Jin-Jun; Xu, Ling

2016-01-27

Traditional Chinese Medicines, unique biomedical and pharmaceutical resources, have been widely used for hepatocellular carcinoma (HCC) prevention and treatment. Accumulated Chinese herb-derived compounds with significant anti-cancer effects against HCC have been identified. Chinese herbal compounds are effective in preventing carcinogenesis, inhibiting cell proliferation, arresting cell cycle, inducing apoptosis, autophagy, cell senescence and anoikis, inhibiting epithelial-mesenchymal transition, metastasis and angiogenesis, regulating immune function, reversing drug resistance and enhancing the effects of chemotherapy in HCC. This paper comprehensively reviews these compounds and their effects on HCC. Finally, the perspectives and rational application of herbal compounds for HCC management are discussed.

A METHOD FOR AUTOMATED ANALYSIS OF 10 ML WATER SAMPLES CONTAINING ACIDIC, BASIC, AND NEUTRAL SEMIVOLATILE COMPOUNDS LISTED IN USEPA METHOD 8270 BY SOLID PHASE EXTRACTION COUPLED IN-LINE TO LARGE VOLUME INJECTION GAS CHROMATOGRAPHY/MASS SPECTROMETRY

EPA Science Inventory

Data is presented showing the progress made towards the development of a new automated system combining solid phase extraction (SPE) with gas chromatography/mass spectrometry for the single run analysis of water samples containing a broad range of acid, base and neutral compounds...

Recent advances in H-phosphonate chemistry. Part 1. H-phosphonate esters: synthesis and basic reactions.

PubMed

Sobkowski, Michal; Kraszewski, Adam; Stawinski, Jacek

2015-01-01

This review covers recent progress in the preparation of H-phosphonate mono- and diesters, basic studies on mechanistic and stereochemical aspects of this class of phosphorus compounds, and their fundamental chemistry in terms of transformation of P-H bonds into P-heteroatom bonds. Selected recent applications of H-phosphonate derivatives in basic organic phosphorus chemistry and in the synthesis of biologically important phosphorus compounds are also discussed.

RLE (Research Laboratory of Electronics) Progress Report Number 129.

DTIC Science & Technology

1987-01-01

8217," ’,/’.’t MICROCOP ,"Y RESOLUTION TEST C-’HA"-/’%’.’."."% "-’- -" "."o -- - -" " OI FILE COPYAJ MASSACHUSETTS INSTITUTE OF EHOGYD The RESEARCH LABORATORY of...Intercalation Compound Structures and Transitions .................................. 59 10.0 Semiconductor Surface Studies...understanding of the HEMT, which is the basic block in building surface superlattices on III-V compound materials, our device structure has been simu

Fabrication of T142 Tank Track Pads for Evaluation of a Rubber-Kevlar Composite Compound

DTIC Science & Technology

1982-06-01

fully developed with highly saturated rubbers such as butyl or ROYALENE® ( EPDM ) A-3 ...PERIOD COVERED Fabrication of T142 Tank Track Pads for Evaluation of a Rubber -Kevlar Composite FINAL Compound S. PERFORMING ORG. REPORT NUMBER 7. AUTHOR...developed for evaluation in T142 tank track pads. Bonding of the rubber to the fiber was achieved by addition of bonding agents to the compound. 175, T142

Chemistry of peroxide compounds

NASA Technical Reports Server (NTRS)

Volnov, I. I.

1981-01-01

The history of Soviet research from 1866 to 1967 on peroxide compounds is reviewed. This research dealt mainly with peroxide kinetics, reactivity and characteristics, peroxide production processes, and more recently with superoxides and ozonides and emphasis on the higher oxides of group 1 and 2 elements. Solid state fluidized bed synthesis and production of high purity products based on the relative solubilities of the initial, intermediate, and final compounds and elements in liquid ammonia are discussed.

Spontaneous regression of curve in immature idiopathic scoliosis - does spinal column play a role to balance? An observation with literature review.

PubMed

Modi, Hitesh N; Suh, Seung-Woo; Yang, Jae-Hyuk; Hong, Jae-Young; Venkatesh, Kp; Muzaffar, Nasir

2010-11-04

Child with mild scoliosis is always a subject of interest for most orthopaedic surgeons regarding progression. Literature described Hueter-Volkmann theory regarding disc and vertebral wedging, and muscular imbalance for the progression of adolescent idiopathic scoliosis. However, many authors reported spontaneous resolution of curves also without any reason for that and the rate of resolution reported is almost 25%. Purpose of this study was to question the role of paraspinal muscle tuning/balancing mechanism, especially in patients with idiopathic scoliosis with early mild curve, for spontaneous regression or progression as well as changing pattern of curves. An observational study of serial radiograms in 169 idiopathic scoliosis children (with minimum follow-up one year) was carried. All children with Cobb angle < 25° and who were diagnosed for the first time were selected. As a sign of immaturity at the time of diagnosis, all children had Risser sign 0. No treatment was given to entire study group. Children were divided in three groups at final follow-up: Group A, B and C as children with regression, no change and progression of their curves, respectively. Additionally changes in the pattern of curve were also noted. Average age was 9.2 years at first visit and 10.11 years at final follow-up with an average follow-up of 21 months. 32.5% (55/169), 41.4% (70/169) and 26% (44/169) children exhibited regression, no change and progression in their curves, respectively. 46.1% of children (78/169) showed changing pattern of their curves during the follow-up visits before it settled down to final curve. Comparing final fate of curve with side of curve and number of curves it did not show any relationship (p > 0.05) in our study population. Possible reason for changing patterns could be better explained by the tuning/balancing mechanism of spinal column that makes an effort to balance the spine and result into spontaneous regression or prevent further progression of curve. If this which we called as "tuning/balancing mechanism" fails, curve will ultimately progress.

Recent Progress and Development of Crystal Structure Analysis of Enzymes and Other Proteins

NASA Astrophysics Data System (ADS)

Tanokura, Masaru; Nagata, Koji; Miyazono, Ken-Ichi; Miyakawa, Takuya; Okai, Masahiko

Structural biology has made tremendous progress in this decade. Here we briefly introduce the Target Proteins Research Program, a national project promoted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. The program aims to reveal the structure and function of proteins that are of great importance in both academic research and industrial application. We also summarize the results of structure-function analyses of (i) transcriptional regulatory proteins useful for the breading of drought and heat stress tolerant crops, (ii) useful enzymes for the production of chiral compounds, and (iii) useful enzymes for the degradation of environmental pollution substances. These results can be utilized in various areas of industries, to enhance food production, to improve the efficiency of pharmaceutical compound production, and to promote the bioremediation of contaminated soil and water.

40 CFR 60.2575 - What are my requirements for meeting increments of progress and achieving final compliance?

Code of Federal Regulations, 2012 CFR

2012-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY... Units Model Rule-Increments of Progress § 60.2575 What are my requirements for meeting increments of...

40 CFR 60.2575 - What are my requirements for meeting increments of progress and achieving final compliance?

Code of Federal Regulations, 2014 CFR

2014-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY... Units Model Rule-Increments of Progress § 60.2575 What are my requirements for meeting increments of...

40 CFR 60.2575 - What are my requirements for meeting increments of progress and achieving final compliance?

Code of Federal Regulations, 2013 CFR

2013-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY... Units Model Rule-Increments of Progress § 60.2575 What are my requirements for meeting increments of...

FINAL Progress Report DOE Grant DE-FG02-04ER15587

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

Mullins, Charles Buddie

Catalysis Program - Viviane Schwartz Program Manager This Final Report discusses several archival journal articles that have been published that present and discuss the results that were discovered through this DOE grant.

78 FR 60226 - Amendments To Implement Certain Provisions of the Moving Ahead for Progress in the 21st Century...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

... Moving Ahead for Progress in the 21st Century Act (MAP-21) AGENCY: Federal Motor Carrier Safety...) adopts, as final, certain regulations required by the Moving Ahead for Progress in the 21st Century... required by MAP-21. Benefits and Costs The rule provisions considered both individually and in the...

Making Progress: The Use of Multiple Progress Reports to Enhance Advertising Students' Media Plan Term Projects

ERIC Educational Resources Information Center

Kritz, Gary H.; Lozada, Hector R.; Long, Mary M.

2007-01-01

Since the AACSB mandates that students demonstrate effective oral and written communication skills, it is imperative that business professors do what is necessary to improve such skills. The authors investigate whether the use of using multiple progress reports in an Advertising class project improves the final product. The data results show that…

78 FR 65705 - Request for Comments on the Annual Progress Report on the Outer Continental Shelf (OCS) Oil and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... (Five Year Program). The Annual Progress Report is available for review at: www.boem.gov/Five-Year-Program-Annual-Progress-Report/ . Information on the Five Year Program is available online at http://www... final on August 27, 2012, after the required 60-day congressional review period. Section 18(e) of the...

Development of genetically engineered bacteria for production of selected aromatic compounds

DOEpatents

Ward, Thomas E.; Watkins, Carolyn S.; Bulmer, Deborah K.; Johnson, Bruce F.; Amaratunga, Mohan

2001-01-01

The cloning and expression of genes in the common aromatic pathway of E. coli are described. A compound for which chorismate, the final product of the common aromatic pathway, is an anabolic intermediate can be produced by cloning and expressing selected genes of the common aromatic pathway and the genes coding for enzymes necessary to convert chorismate to the selected compound. Plasmids carrying selected genes of the common aromatic pathway are also described.

Microbial diversity and their roles in the vinegar fermentation process.

PubMed

Li, Sha; Li, Pan; Feng, Feng; Luo, Li-Xin

2015-06-01

Vinegar is one of the oldest acetic acid-diluted solution products in the world. It is produced from any fermentable sugary substrate by various fermentation methods. The final vinegar products possess unique functions, which are endowed with many kinds of compounds formed in the fermentation process. The quality of vinegar is determined by many factors, especially by the raw materials and microbial diversity involved in vinegar fermentation. Given that metabolic products from the fermenting strains are directly related to the quality of the final products of vinegar, the microbial diversity and features of the dominant strains involved in different fermentation stages should be analyzed to improve the strains and stabilize fermentation. Moreover, although numerous microbiological studies have been conducted to examine the process of vinegar fermentation, knowledge about microbial diversity and their roles involved in fermentation is still fragmentary and not systematic enough. Therefore, in this review, the dominant microorganism species involved in the stages of alcoholic fermentation and acetic acid fermentation of dissimilar vinegars were summarized. We also summarized various physicochemical properties and crucial compounds in disparate types of vinegar. Furthermore, the merits and drawbacks of vital fermentation methods were generalized. Finally, we described in detail the relationships among microbial diversity, raw materials, fermentation methods, physicochemical properties, compounds, functionality, and final quality of vinegar. The integration of this information can provide us a detailed map about the microbial diversity and function involved in vinegar fermentation.

Heterogeneous photocatalytic oxidation of atmospheric trace contaminants

NASA Technical Reports Server (NTRS)

Ollis, David F.; Peral, Jose

1992-01-01

A two year study to examine the feasibility of using heterogeneous photocatalysis for spacecraft air purification was begun at North Carolina State University on November 1, 1990. The original grant proposal included examination of the rates of destruction of anticipated spacecraft-generated air contaminants, including alcohols, aldehydes, chlorinated compounds, as well as trace levels of volatile compounds containing nitrogen, sulfur, and silicon. The progress made in the second six month period of 5/1/91-11/1/91 is discussed.

Feasibility of Active Machine Learning for Multiclass Compound Classification.

PubMed

Lang, Tobias; Flachsenberg, Florian; von Luxburg, Ulrike; Rarey, Matthias

2016-01-25

A common task in the hit-to-lead process is classifying sets of compounds into multiple, usually structural classes, which build the groundwork for subsequent SAR studies. Machine learning techniques can be used to automate this process by learning classification models from training compounds of each class. Gathering class information for compounds can be cost-intensive as the required data needs to be provided by human experts or experiments. This paper studies whether active machine learning can be used to reduce the required number of training compounds. Active learning is a machine learning method which processes class label data in an iterative fashion. It has gained much attention in a broad range of application areas. In this paper, an active learning method for multiclass compound classification is proposed. This method selects informative training compounds so as to optimally support the learning progress. The combination with human feedback leads to a semiautomated interactive multiclass classification procedure. This method was investigated empirically on 15 compound classification tasks containing 86-2870 compounds in 3-38 classes. The empirical results show that active learning can solve these classification tasks using 10-80% of the data which would be necessary for standard learning techniques.

[Carbonyl compounds emission and uptake by plant: Research progress].

PubMed

Li, Jian; Cai, Jing; Yan, Liu-Shui; Li, Ling-Na; Tao, Min

2013-02-01

This paper reviewed the researches on the carbonyl compounds emission and uptake by plants, and discussed the compensation point of the bidirectional exchange of carbonyl compounds between plants and atmosphere. The uptake by leaf stomata and stratum corneum is the principal way for the purification of air aldehydes by plants. After entering into plant leaves, most parts of carbonyl compounds can be metabolized into organic acid, glucide, amino acid, and carbon dioxide, etc. , by the endoenzymes in leaves. The exchange direction of the carbonyl compounds between plants and atmosphere can be preliminarily predicted by the compensation point and the concentrations of ambient carbonyl compounds. This paper summarized the analytical methods such as DNPH/HPLC/UV and PFPH/GC/MS used for the determination of carbonyl compounds emitted from plants or in plant leaves. The main research interests in the future were pointed out, e. g. , to improve and optimize the analytical methods for the determination of carbonyl compounds emitted from plants and the researches on systems (e. g. , plant-soil system), to enlarge the detection species of carbonyl compounds emitted from plants, to screen the plant species which can effectively metabolize the pollutants, and to popularize the phytoremediation techniques for atmospheric

Microwave-assisted one-pot synthesis of new phenanthrene fused-tetrahydrodibenzo-acridinones as potential cytotoxic and apoptosis inducing agents.

PubMed

Kumar, Niggula Praveen; Sharma, Pankaj; Reddy, T Srinivasa; Shankaraiah, Nagula; Bhargava, Suresh K; Kamal, Ahmed

2018-05-10

An expeditious microwave-assisted one-pot synthesis of new cytotoxic phenanthrene fused-tetrahydrodibenzo-acridinones has been successfully accomplished. This protocol offers wide substrate scope, catalyst-free synthesis, atom-economy, simple recrystallization, high yields, and ethanol was used as green solvent. These new compounds were tested for their in vitro cytotoxicity against cervical (HeLa), prostate (PC-3), fibrosarcoma (HT-1080), ovarian (SKOV-3) cancer cells, and were safer to normal (Hek-293T) kidney cell line. All the compounds have displayed significant cytotoxicity profile, among them 8m being the most potent compound with an IC 50 0.24 ± 0.05 μM against SKOV-3 ovarian cancer cells. Flow cytometry analysis revealed that cells were blocked at the G2/M phase of the cell cycle. The effect of 8m on F-actin polymerisation was also studied. Hoechst staining clearly showed the decreased number of viable cells and indicated apoptosis progression. Compound 8m caused the collapse of mitochondrial membrane potential as observed via JC-1 staining and also enhanced the generation of reactive oxygen species. The increase of caspase-3 activation by 3.7 folds supported the strong apoptosis induction. In addition, an in vitro 3D-spheroid progression assay was performed with 8m that significantly suppressed the tumor cells. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Bioactives in Chinese Proprietary Medicine Modulates 5α-Reductase Activity and Gene Expression Associated with Androgenetic Alopecia

PubMed Central

Tan, Justin J. Y.; Pan, Jing; Sun, Lihan; Zhang, Junying; Wu, Chunyong; Kang, Lifeng

2017-01-01

Androgenetic alopecia (AGA) is characterized by a progressive and patterned transformation of thick, pigmented terminal scalp hairs into short, hypo-pigmented vellus-like hairs. The use of Minoxidil and Finasteride to treat AGA are often associated with complications in safety and efficacy. However, herbal remedies are deemed to have lesser side effects in many societies. This study aims to identify potential hair growth properties of individual compounds from a Chinese proprietary medicine known as Yangxue Shengfa capsule (YSC), used in China for many years for improving AGA. Six marker compounds, including 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), Chlorogenic acid, Emodin, Ferulic acid, Isoimperatorin, and Paeoniflorin were used for simultaneous HPLC quantification and anti-AGA in-vitro screening. Simultaneous quantification of these components was performed on 75% (v/v) methanol extracts of YSC, using a Welch Ultimate XB-C18 column and gradient elution. Five compounds significantly promoted cell proliferation in cultured immortalized human Dermal Papilla Cells (DPC). Multiple genes associated with the progression of AGA, including IGF-1, DKK-1, and TGF-β1, were found to be regulated by some of these compounds. Interestingly, Ferulic acid and Emodin demonstrated good pharmacological properties against AGA, thereby concluding the potential of these bioactives to be used in the treatment against AGA. PMID:28450835

Microcomputer-Assisted Mathematics: From Simple Interest to e.

ERIC Educational Resources Information Center

Kimberling, Clark

1985-01-01

The progression from simple interest to compound interest leads naturally and quickly to the number e, involving mathematical discovery learning through writing programs. Several programs are given, with suggestions for a teaching sequence. (MNS)

TESL Reporter, Vol. 3, Nos. 1-4.

ERIC Educational Resources Information Center

Pack, Alice C., Ed.

Four issues of "TESL Reporter" are presented. Contents include the following articles: "Feedback: An Anti-Madeirization Compound" by Henry M. Schaafsma; "Using the Personal Pronoun 'I' as a Compound Subject" by G. Pang and D. Chu; "The Consonant'L' in Initial and Final Positions" by Maybelle Chong; "Sentence Expansion for the Elementary Level" by…

Effect of sinapic acid on hair growth promoting in human hair follicle dermal papilla cells via Akt activation.

PubMed

Woo, Hyunju; Lee, Seungjun; Kim, Seungbeom; Park, Deokhoon; Jung, Eunsun

2017-07-01

Hair loss known as alopecia is caused by abnormal hair follicle cycling including shortening of the anagen (growth) phase and changing of hair follicle morphology with miniaturization. In accordance with the life extension, the quality of life is considered to be a most important thing. The yearning for healthy and beautiful hair and low self esteem due to hair loss had negative influence on the quality of life with psychosocial maladjustment. The objective of this research was to identify new compound that can be used as a drug to promote hair growth. We investigated whether the function of sinapic acid (SA) is able to promote hair growth in human hair follicle dermal papilla cells (hHFDPC). We showed that treatment of SA in hHFDPC could induce proliferation and the activation of Akt signaling in HFDPC. In addition, SA could stimulate the expressions of the several growth factors, insulin-like growth factor 1, and vascular endothelial growth factor for hair growth. We showed that SA led to an increased level of phospho-GSK-3β and β-catenin accumulation in HFDPC. Finally, the promoting effect of SA in hHFDPC cell growth occurred by the induction of cell cycle progression. These results suggest that SA could be one of the potential candidate compounds for the treatment of alopecia by inducing hair growth through triggering the expressions of growth factors via activation of Akt and subsequent inactivation of GSK-3β /β-catenin pathway.

The seleno-organic compound ebselen impairs mitochondrial physiology and induces cell death in AR42J cells.

PubMed

Santofimia-Castaño, Patricia; Garcia-Sanchez, Lourdes; Ruy, Deborah Clea; Fernandez-Bermejo, Miguel; Salido, Gines M; Gonzalez, Antonio

2014-09-17

Ebselen is a seleno-organic compound that causes cell death in several cancer cell types. The mechanisms underlying its deleterious effects have not been fully elucidated. In this study, the effects of ebselen (1 μM-40 μM) on AR42J tumor cells have been examined. Cell viability was studied using AlamarBlue(®) test. Cell cycle phase determination was carried out by flow cytometry. Changes in intracellular free Ca(2+) concentration were followed by fluorimetry analysis of fura-2-loaded cells. Distribution of mitochondria, mitochondrial Ca(2+) concentration and mitochondrial membrane potential were monitored by confocal microscopy of cells loaded with Mitotracker Green™ FM, rhod-2 or TMRM respectively. Caspase-3 activity was calculated following the luorogenic substrate ACDEVD-AMC signal with a spectrofluorimeter. Results show that cell viability decreased in the presence of ebselen. An increase in the number of cells in the S-phase of the cell cycle was observed. Ebselen induced a concentration-dependent mobilization of Ca(2+) from agonist- and thapsigargin-sensitive Ca(2+) pools. Ebselen induced also a transient increase in mitochondrial Ca(2+) concentration, a progressive decrease of the mitochondrial membrane potential and a disruption of the mitochondrial network. Finally, a concentration-dependent increase in caspase-3 activity was detected. We conclude that ebselen exerts deleterious actions on the cells that involve the impairment of mitochondrial physiology and the activation of caspase-3-mediated apoptotic pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Tech Prep II: Implementation Final Report.

ERIC Educational Resources Information Center

Brown, Jane A.

This document contains the final progress report on a tech prep implementation project and the Work Force Challenge 2000 Report developed during the project. The final report lists these major accomplishments: approximately 1,500 educators in grades K-12 were provided information concerning future global issues in the work force and the effects in…

40 CFR 60.1585 - What are my requirements for meeting increments of progress and achieving final compliance?

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY... or Before August 30, 1999 Model Rule-Increments of Progress § 60.1585 What are my requirements for...

RECENT PROGRESS IN GLYCOCHEMISTRY AND GREEN CHEMISTRY. (R826123)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Compound matrices

NASA Astrophysics Data System (ADS)

Kravvaritis, Christos; Mitrouli, Marilena

2009-02-01

This paper studies the possibility to calculate efficiently compounds of real matrices which have a special form or structure. The usefulness of such an effort lies in the fact that the computation of compound matrices, which is generally noneffective due to its high complexity, is encountered in several applications. A new approach for computing the Singular Value Decompositions (SVD's) of the compounds of a matrix is proposed by establishing the equality (up to a permutation) between the compounds of the SVD of a matrix and the SVD's of the compounds of the matrix. The superiority of the new idea over the standard method is demonstrated. Similar approaches with some limitations can be adopted for other matrix factorizations, too. Furthermore, formulas for the n - 1 compounds of Hadamard matrices are derived, which dodge the strenuous computations of the respective numerous large determinants. Finally, a combinatorial counting technique for finding the compounds of diagonal matrices is illustrated.

Prebiotics: application in bakery and pasta products.

PubMed

Padma Ishwarya, S; Prabhasankar, P

2014-01-01

The concept of functional foods has markedly moved toward gastrointestinal health. The prebiotic approach aims at achieving favorable milieu in the human gut by stimulating beneficial bacteria. Several food products act as substrates for the application of prebiotic substances and bakery products are one such category. The trend of increasing consumption of bakery products justifies the choice of using them as vehicles for delivering the prebiotic compounds. Apart from the health benefits, the prebiotic compounds also have nutritional and technological effects in the food matrix. In addition to increasing the fiber content, the candidate prebiotics also affect the rheology and final quality of bakery products. The prebiotic compounds are selected accordingly to confer desirable properties in the final product. The health advantages of prebiotics being well established, the technological advantages in bakery products such as bread and biscuits and extruded product such as pasta are discussed elaborately.

PREVENTION OF COLITIS-ASSOCIATED CANCER: NATURAL COMPOUNDS THAT TARGET THE IL-6 SOLUBLE RECEPTOR

PubMed Central

Moriasi, Cate; Subramaniam, Dharmalingam; Awasthi, Shanjana; Anant, Shrikant; Ramalingam, Satish

2014-01-01

The risk of developing colorectal cancer increases in patients with inflammatory bowel disease (IBD) and a growing body of evidence shows the critical role of interleukin (IL-6) in this process. IL-6 is both a pro- and anti-inflammatory cytokine whose effects are mediated through activation of STAT3. Recent studies have also demonstrated that IL-6 trans-signaling through its soluble receptor occurs in IBD and cancer. IL-6 trans-signaling therefore is emerging as an attractive approach to diminish the inflammatory signals in conditions of chronic inflammation. The purpose of cancer chemoprevention is to either delay the onset or progression from precancerous lesions. Natural compounds because of their low toxicity render themselves excellent candidates that can be administered over the lifetime of an individual. With the focus of managing IBD over a long time and preventing onset of colitis-associated cancer, we believe that there should be increased research focus on identifying chemopreventive compounds that can render themselves to long term use possibly for the lifetime of predisposed individuals. Here, we review the role of IL-6 signaling in IBD and colitis-associated cancer and underscore the importance of searching for natural compounds that would target the IL-6 trans-signaling pathway as a way to diminish chronic inflammatory conditions in the gastrointestinal tract and possibly hamper the progression to colon cancer. We propose that effective screening and identification of natural chemopreventive compounds that target IL-6 trans-signaling has important implications for the development of optimal strategies against cancer development triggered by inflammation. PMID:22583410

Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets

PubMed Central

Siles-Lucas, Mar; Casulli, Adriano; Cirilli, Roberto

2018-01-01

Human cystic and alveolar echinococcosis are helmintic zoonotic diseases caused by infections with the larval stages of the cestode parasites Echinococcus granulosus and E. multilocularis, respectively. Both diseases are progressive and chronic, and often fatal if left unattended for E. multilocularis. As a treatment approach, chemotherapy against these orphan and neglected diseases has been available for more than 40 years. However, drug options were limited to the benzimidazoles albendazole and mebendazole, the only chemical compounds currently licensed for treatment in humans. To compensate this therapeutic shortfall, new treatment alternatives are urgently needed, including the identification, development, and assessment of novel compound classes and drug targets. Here is presented a thorough overview of the range of compounds that have been tested against E. granulosus and E. multilocularis in recent years, including in vitro and in vivo data on their mode of action, dosage, administration regimen, therapeutic outcomes, and associated clinical symptoms. Drugs covered included albendazole, mebendazole, and other members of the benzimidazole family and their derivatives, including improved formulations and combined therapies with other biocidal agents. Chemically synthetized molecules previously known to be effective against other infectious and non-infectious conditions such as anti-virals, antibiotics, anti-parasites, anti-mycotics, and anti-neoplastics are addressed. In view of their increasing relevance, natural occurring compounds derived from plant and fungal extracts are also discussed. Special attention has been paid to the recent application of genomic science on drug discovery and clinical medicine, particularly through the identification of small inhibitor molecules tackling key metabolic enzymes or signalling pathways. PMID:29677189

Bulk Viscoelastic Contribution to the Wet Sliding Friction of Rubber Compounds

NASA Astrophysics Data System (ADS)

Pan, Xiao-Dong

2002-03-01

An efficient stopping of an automobile on a wet highway in a rainy day is of obvious importance to the safety of the driving public. Here tire tread made of filled rubber compounds plays an essential role in detremining the wet traction performance. Even though significant progress has been made in improving this tire performance character and much knowledge has been accumulated, there still lacks a coherent fundamental understanding on this dynamic process. Consequently there currently exist no accurate guidelines for designing rubber compounds for better wet traction, and for predicting the wet traction performance of a rubber compound. In this experimental study, a portable British Pendulum Skid Tester has been employed to examine in the laboratory how the rubber compound material properties affect its wet sliding friction on a concrete surface. A dramatic dispaly of the impacts from the compound bulk viscoelastic properties has been observed for the first time. This observation will be discussed in relation to previous results discussed in the literature.

Statistical Research on the Bioactivity of New Marine Natural Products Discovered during the 28 Years from 1985 to 2012

PubMed Central

Hu, Yiwen; Chen, Jiahui; Hu, Guping; Yu, Jianchen; Zhu, Xun; Lin, Yongcheng; Chen, Shengping; Yuan, Jie

2015-01-01

Every year, hundreds of new compounds are discovered from the metabolites of marine organisms. Finding new and useful compounds is one of the crucial drivers for this field of research. Here we describe the statistics of bioactive compounds discovered from marine organisms from 1985 to 2012. This work is based on our database, which contains information on more than 15,000 chemical substances including 4196 bioactive marine natural products. We performed a comprehensive statistical analysis to understand the characteristics of the novel bioactive compounds and detail temporal trends, chemical structures, species distribution, and research progress. We hope this meta-analysis will provide useful information for research into the bioactivity of marine natural products and drug development. PMID:25574736

Anticancer effects of different seaweeds on human colon and breast cancers.

PubMed

Moussavou, Ghislain; Kwak, Dong Hoon; Obiang-Obonou, Brice Wilfried; Maranguy, Cyr Abel Ogandaga; Dinzouna-Boutamba, Sylvatrie-Danne; Lee, Dae Hoon; Pissibanganga, Ordelia Gwenaelle Manvoudou; Ko, Kisung; Seo, Jae In; Choo, Young Kug

2014-09-24

Seafoods and seaweeds represent some of the most important reservoirs of new therapeutic compounds for humans. Seaweed has been shown to have several biological activities, including anticancer activity. This review focuses on colorectal and breast cancers, which are major causes of cancer-related mortality in men and women. It also describes various compounds extracted from a range of seaweeds that have been shown to eradicate or slow the progression of cancer. Fucoidan extracted from the brown algae Fucus spp. has shown activity against both colorectal and breast cancers. Furthermore, we review the mechanisms through which these compounds can induce apoptosis in vitro and in vivo. By considering the ability of compounds present in seaweeds to act against colorectal and breast cancers, this review highlights the potential use of seaweeds as anticancer agents.

Computational Methods for Nonlinear Dynamic Problems in Solid and Structural Mechanics: Progress in the Theory and Modeling of Friction and in the Control of Dynamical Systems with Frictional Forces

DTIC Science & Technology

1989-03-31

present several numerical studies designed to reveal the effect that some of the governing parameters have on the behavior of the system and, whenever...Friction and in the Control of Dynamical Systems with Frictional Forces FINAL TECHNICAL REPORT March 31, 1989 _ -- I -.7: .-.- - : AFOSR Contract F49620...SOLID AND STRUCTURAL MECHANICS: Progress in the Theory and Modeling of Friction and in the Control of Dynamical Systems with Frictional Forces I I * FINAL

The use of Aotus Trivirgatus and Macaca Mulatta as Tools for Studies on Prevention and Therapy of Infections with Plasmodium Falciparum and Plasmodium Vivax

DTIC Science & Technology

1976-08-13

INFECTIONS WITH PLASMODIUM FALCIPARUM AND PLASMODIUM VIVAX (U) FINAL PROGRESS REPORT ( PROJECT 2284-XXIX) For the Period I May 1975 to 30 April...IT» IOC mit settiM I’jtf Section ^ I» ’■■■■• BisTtmunM/MWUiiun cooa DiJÜ iWBU. UK/» FINAL PROGRESS REPORT ( PROJECT 2284-XXIX) S...quinolinemethanols pyridinemethanols I ’As in previous years, the activities of this Project were focused on development of: (a) agents fully effective

Genistein versus ICI 182, 780: an ally or enemy in metastatic progression of prostate cancer.

PubMed

Nakamura, Hisae; Wang, Yuwei; Xue, Hui; Romanish, Mark T; Mager, Dixie L; Helgason, Cheryl D; Wang, Yuzhuo

2013-12-01

Androgen signalling through the androgen receptor (AR) plays a critical role in prostate cancer (PCa) initiation and progression. Estrogen in synergy with androgen is essential for cell growth of the normal and malignant prostate. However, the exact role that estrogen and the estrogen receptor play in prostate carcinogenesis remains unclear. We have previously demonstrated the metastasis-promoting effect of an estrogen receptor beta (ERβ) agonist (genistein) in a patient-derived PCa xenograft model mimicking localized and metastatic disease. To test the hypothesis that the tumor-promoting activity of genistein was due to its estrogenic properties, we treated the xenograft-bearing mice with genistein and an anti-estrogen compound (ICI 182, 780) and compared the differential gene expression using microarrays. Using a second xenograft model which was derived from another patient, we showed that genistein promoted disease progression in vivo and ICI 182, 780 inhibited metastatic spread. The microarray analysis revealed that the metallothionein (MT) gene family was differentially expressed in tumors treated by these compounds. Using qRT-PCR, the differences in expression levels were validated in the metastatic and non-metastatic LTL313 PCa xenograft tumor lines, both of which were originally derived from the same PCa patient. Together our data provide evidence that genistein stimulates and ICI 182, 780 inhibits metastatic progression, suggesting that these effects may be mediated by ERβ signalling. © 2013 Wiley Periodicals, Inc.

40 CFR 60.1630 - How do I comply with the increment of progress for achieving final compliance?

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES... Before August 30, 1999 Model Rule-Increments of Progress § 60.1630 How do I comply with the increment of...

75 FR 6012 - National Assessment of Educational Progress (NAEP) in Reading

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-05

... comment for evaluating and finalizing achievement levels definitions for the National Assessment of... comment and recommendations for improvements to the achievement levels definitions for the National Assessment of Educational Progress (NAEP) in reading. These achievement levels definitions describe the...

Elucidation of key aroma compounds in traditional dry fermented sausages using different extraction techniques.

PubMed

Corral, Sara; Salvador, Ana; Flores, Mónica

2015-04-01

The use of different extraction techniques - solid phase microextraction (SPME) and solvent assisted flavour evaporation (SAFE) - can deliver different aroma profiles and it is essential to determine which is most suitable to extract the aroma compounds from dry fermented sausages. Forty-five aroma-active compounds were detected by SPME and SAFE, with 11 of them reported for the first time as aroma compounds in dry fermented sausages: ethyl 3-hydroxy butanoate, trimethyl pyrazine, D-pantolactone, isobutyl hexanoate, ethyl benzoate, α-terpineol, ethyl 3-pyridinecarboxylate, benzothiazole, 2,3-dihydrothiophene, methyl eugenol, γ-nonalactone. The aroma concentration and odour activity values (OAVs) were calculated. Flavour reconstitution analyses were performed using 20 odorants with OAVs above 1 obtained from the SAFE and SPME extracts to prepare the aroma model. SPME and SAFE techniques were complementary and necessary to reproduce the overall dry fermented sausage aroma. The final aroma model included the odorants from both extraction techniques (SPME and SAFE) but it was necessary to incorporate the compounds 2,4-decadienal (E,E), benzothiazole, methyl eugenol, α-terpineol, and eugenol to the final aroma model to evoked the fresh sausage aroma although a lowest cured meat aroma note was perceived. © 2014 Society of Chemical Industry.

Compound 49b Reduces Inflammatory Markers and Apoptosis after Ocular Blast Injury

DTIC Science & Technology

2015-11-01

provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid...finalize the testing of Compound 49b in the IGBP-3 pathway in a trauma model. Specifically, we have done experimentation on how the inflammatory...effects of Compound 49b after ocular blast injury and successfully generated a method for the isolation of retinal ganglion cells, which are critical

Proceedings of the Tri-Service Conference on Corrosion Held in Atlantic City, New Jersey on 17-19 October 1989

DTIC Science & Technology

1989-10-19

installation. 4. Corrosion inhibiting compounds need to be applied in the final assealbly of models to all corrosion prone areas of the structure, e.g...Figure 12 shows an example of poor surface treatment of a previously repaired stringer area. Application of a corrosion inhibiting compound may have... compounds and a good corrosion control maintenance program. REFERENCE U. G. Goranson and M. Miller, "Aging Fleet - Aging Fleet Evaluation Program

Extraction, chemical characterization and biological activity determination of broccoli health promoting compounds.

PubMed

Ares, Ana M; Nozal, María J; Bernal, José

2013-10-25

Broccoli (Brassica oleracea L. var. Italica) contains substantial amount of health-promoting compounds such as vitamins, glucosinolates, phenolic compounds, and dietary essential minerals; thus, it benefits health beyond providing just basic nutrition, and consumption of broccoli has been increasing over the years. This review gives an overview on the extraction and separation techniques, as well as the biological activity of some of the above mentioned compounds which have been published in the period January 2008 to January 2013. The work has been distributed according to the different families of health promoting compounds discussing the extraction procedures and the analytical techniques employed for their characterization. Finally, information about the different biological activities of these compounds has been also provided. Copyright © 2013 Elsevier B.V. All rights reserved.

Material aid for vaccines

NASA Astrophysics Data System (ADS)

Irvine, Darrell

2018-06-01

Darrell Irvine provides an overview of the recent advances in materials science that have enabled the use of innovative natural and synthetic compounds in vaccine development capable of regulating the potency and safety of new vaccines progressing towards the clinic.

PATHOPHYSIOLOGICAL PROGRESSION AND RELATIONSHIPS FOR SELECTED ENDPOINTS

EPA Science Inventory

The Environmental Protection Agency (EPA), Office of Research and Development (ORD), National Center for Environmental Assessment (NCEA) is currently developing methodologies and information sources to use as guidelines for acute exposure to various compounds, including air toxic...

A clue to unprecedented strategy to HIV eradication: “Lock-in and apoptosis”

DOE PAGES

Tateishi, Hiroshi; Monde, Kazuaki; Anraku, Kensaku; ...

2017-08-21

Despite the development of antiretroviral therapy against HIV, eradication of the virus from the body, as a means to a cure, remains in progress. A “kick and kill” strategy proposes “kick” of the latent HIV to an active HIV to eventually be “killed”. Latency-reverting agents that can perform the “kick” function are under development and have shown promise. Management of the infected cells not to produce virions after the “kick” step is important to this strategy. Here we show that a newly synthesized compound, L-HIPPO, captures the HIV-1 protein Pr55Gag and intercepts its function to translocate the virus from themore » cytoplasm to the plasma membrane leading to virion budding. The infecting virus thus “locked-in” subsequently induces apoptosis of the host cells. This “lock-in and apoptosis” approach performed by our novel compound in HIV-infected cells provides a means to bridge the gap between the “kick” and “kill” steps of this eradication strategy. By building upon previous progress in latency reverting agents, our compound appears to provide a promising step toward the goal of HIV eradication from the body« less

Progress report on new antiepileptic drugs: A summary of the Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII).

PubMed

Bialer, Meir; Johannessen, Svein I; Levy, René H; Perucca, Emilio; Tomson, Torbjörn; White, H Steve

2017-02-01

The Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII) took place in Madrid, Spain, on June 26-29, 2016, and was attended by >200 delegates from 31 countries. The present Progress Report provides an update on experimental and clinical results for drugs presented at the Conference. Compounds for which summary data are presented include an AED approved in 2016 (brivaracetam), 12 drugs in phase I-III clinical development (adenosine, allopregnanolone, bumetanide, cannabidiol, cannabidivarin, 2-deoxy-d-glucose, everolimus, fenfluramine, huperzine A, minocycline, SAGE-217, and valnoctamide) and 6 compounds or classes of compounds for which only preclinical data are available (bumetanide derivatives, sec-butylpropylacetamide, FV-082, 1OP-2198, NAX 810-2, and SAGE-689). Overall, the results presented at the Conference show that considerable efforts are ongoing into discovery and development of AEDs with potentially improved therapeutic profiles compared with existing agents. Many of the drugs discussed in this report show innovative mechanisms of action and many have shown promising results in patients with pharmacoresistant epilepsies, including previously neglected rare and severe epilepsy syndromes. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of FARS2-Linked Disease.

PubMed

Walker, Melissa A; Mohler, Kyle P; Hopkins, Kyle W; Oakley, Derek H; Sweetser, David A; Ibba, Michael; Frosch, Matthew P; Thibert, Ronald L

2016-08-01

Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins. © The Author(s) 2016.

A clue to unprecedented strategy to HIV eradication: “Lock-in and apoptosis”

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

Tateishi, Hiroshi; Monde, Kazuaki; Anraku, Kensaku

Despite the development of antiretroviral therapy against HIV, eradication of the virus from the body, as a means to a cure, remains in progress. A “kick and kill” strategy proposes “kick” of the latent HIV to an active HIV to eventually be “killed”. Latency-reverting agents that can perform the “kick” function are under development and have shown promise. Management of the infected cells not to produce virions after the “kick” step is important to this strategy. Here we show that a newly synthesized compound, L-HIPPO, captures the HIV-1 protein Pr55Gag and intercepts its function to translocate the virus from themore » cytoplasm to the plasma membrane leading to virion budding. The infecting virus thus “locked-in” subsequently induces apoptosis of the host cells. This “lock-in and apoptosis” approach performed by our novel compound in HIV-infected cells provides a means to bridge the gap between the “kick” and “kill” steps of this eradication strategy. By building upon previous progress in latency reverting agents, our compound appears to provide a promising step toward the goal of HIV eradication from the body« less

Adhesives, fillers and potting compounds. Second progress report, December 1, 1967--April 1, 1968

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

Lichte, H.W.; Akst, I.B.

1968-12-31

Progress in the development program whose immediate purpose is to reduce set time of a silicone compound is described. Data are presented showing that a formulation of a current RTV silicone rubber with dibutyltin diacetate has a profitably lower set time than the same rubber in the present formulation which uses dibutyltin dilaurate, without increase in probability of either reversion or penalty to other weapons components. Time to set sufficiently to allow the next assembly step is 2 to 4 hours, compared to the 16 to 24 hours presently allowed or the 8 to 12 hours minimum attainable with themore » present formulation. The reduction is of the magnitude set as a goal, the attainment of which would increase production capacity enough to reduce the amount of new construction planned to accommodate weapons assembly programs.« less

Enhancing the Health-Promoting Effects of Tomato Fruit for Biofortified Food

PubMed Central

Rigano, Maria Manuela; Frusciante, Luigi; Barone, Amalia

2014-01-01

Consumption of tomato fruits, like those of many other plant species that are part of the human diet, is considered to be associated with several positive effects on health. Indeed, tomato fruits are an important source of bioactive compounds with known beneficial effects including vitamins, antioxidants, and anticancer substances. In particular, antioxidant metabolites are a group of vitamins, carotenoids, phenolic compounds, and phenolic acid that can provide effective protection by neutralizing free radicals, which are unstable molecules linked to the development of a number of degenerative diseases and conditions. In this review, we will summarize the recent progress on tomatoes nutritional importance and mechanisms of action of different phytochemicals against inflammation processes and prevention of chronic noncommunicable diseases (e.g., obesity, diabetes, coronary heart disease, and hypertension). In addition, we will summarize the significant progress recently made to improve the nutritional quality of tomato fruits through metabolic engineering and/or breeding. PMID:24744504

Anti-inflammatory agents from plants: progress and potential.

PubMed

Recio, M C; Andujar, I; Rios, J L

2012-01-01

The identification of substances that can promote the resolution of inflammation in a way that is homeostatic, modulatory, efficient, and well-tolerated by the body is of fundamental importance. Traditional medicines have long provided front-line pharmacotherapy for many millions of people worldwide. Medicinal extracts are a rich source of therapeutic leads for the pharmaceutical industry. The use of medicinal plant therapies to treat chronic illness, including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), is thus widespread and on the rise.The aim of this review is to present recent progress in clinical anti-inflammatory studies of plant extracts and compound leads such as green tea polyphenols, curcumin, resveratrol, boswellic acid, and cucurbitacins, among others, against chronic inflammatory diseases, mainly RA and IBD. In this context, the present paper also highlights the most promising experimental data on those plant extracts and pure compounds active in animal models of the aforementioned diseases.

Mechanisms for radiation damage in DNA. Progress report, January 1, 1980-December 31, 1980

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

Sevilla, M D

1980-09-01

In this project several mechanisms are proposed for radiation damage to DNA constituents and DNA, and a series of experiments detailed utilizing electron spin resonance spectrometry to test the proposed mechanisms. Under current investigation are irradiated systems of DNA constituents which may shed light on indirect effects. In addition, studies of radiation effects on lipids have been undertaken which will shed light on the only other proposed site for cell kill, the membrane. Studies completed during the past year are: (1) ..pi.. cations produced in DNA bases by attack of oxidizing radicals; (2) INDO studies of radicals produced in peptidesmore » and carboxylic acid model compounds; (3) electron reactions with carboxylic acids, ketones and aldehydes; and (4) ..gamma..-irradiation of esters and triglycerides. Progress has been made this year in a study of radicals generated in model compounds for the sugar-phosphate backbone.« less

Preventive Effects of Cocoa and Cocoa Antioxidants in Colon Cancer

PubMed Central

Martín, María Angeles; Goya, Luis; Ramos, Sonia

2016-01-01

Colorectal cancer is one of the main causes of cancer-related mortality in the developed world. Carcinogenesis is a multistage process conventionally defined by the initiation, promotion and progression stages. Natural polyphenolic compounds can act as highly effective antioxidant and chemo-preventive agents able to interfere at the three stages of cancer. Cocoa has been demonstrated to counteract oxidative stress and to have a potential capacity to interact with multiple carcinogenic pathways involved in inflammation, proliferation and apoptosis of initiated and malignant cells. Therefore, restriction of oxidative stress and/or prevention or delayed progression of cancer stages by cocoa antioxidant compounds has gained interest as an effective approach in colorectal cancer prevention. In this review, we look over different in vitro and in vivo studies that have identified potential targets and mechanisms whereby cocoa and their flavonoids could interfere with colonic cancer. In addition, evidence from human studies is also illustrated. PMID:28933386

Recent progress on biomass co-pyrolysis conversion into high-quality bio-oil.

PubMed

Hassan, H; Lim, J K; Hameed, B H

2016-12-01

Co-pyrolysis of biomass with abundantly available materials could be an economical method for production of bio-fuels. However, elimination of oxygenated compounds poses a considerable challenge. Catalytic co-pyrolysis is another potential technique for upgrading bio-oils for application as liquid fuels in standard engines. This technique promotes the production of high-quality bio-oil through acid catalyzed reduction of oxygenated compounds and mutagenic polyaromatic hydrocarbons. This work aims to review and summarize research progress on co-pyrolysis and catalytic co-pyrolysis, as well as their benefits on enhancement of bio-oils derived from biomass. This review focuses on the potential of plastic wastes and coal materials as co-feed in co-pyrolysis to produce valuable liquid fuel. This paper also proposes future directions for using this technique to obtain high yields of bio-oils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel Psychoactive Substances-Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs.

PubMed

Hassan, Zurina; Bosch, Oliver G; Singh, Darshan; Narayanan, Suresh; Kasinather, B Vicknasingam; Seifritz, Erich; Kornhuber, Johannes; Quednow, Boris B; Müller, Christian P

2017-01-01

A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug's properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine ("Kratom"), synthetic cannabinoids (e.g., "Spice"), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications.

Prediction of pH-Dependent Hydrophobic Profiles of Small Molecules from Miertus-Scrocco-Tomasi Continuum Solvation Calculations.

PubMed

Zamora, William J; Curutchet, Carles; Campanera, Josep M; Luque, F Javier

2017-10-26

Hydrophobicity is a key physicochemical descriptor used to understand the biological profile of (bio)organic compounds as well as a broad variety of biochemical, pharmacological, and toxicological processes. This property is estimated from the partition coefficient between aqueous and nonaqueous environments for neutral compounds (P N ) and corrected for the pH-dependence of ionizable compounds as the distribution coefficient (D). Here, we have extended the parametrization of the Miertus-Scrocco-Tomasi continuum solvation model in n-octanol to nitrogen-containing heterocyclic compounds, as they are present in many biologically relevant molecules (e.g., purines and pyrimidines bases, amino acids, and drugs), to obtain accurate log P N values for these molecules. This refinement also includes solvation calculations for ionic species in n-octanol with the aim of reproducing the experimental partition of ionic compounds (P I ). Finally, the suitability of different formalisms to estimate the distribution coefficient for a wide range of pH values has been examined for a set of small acidic and basic compounds. The results indicate that in general the simple pH-dependence model of the ionizable compound in water suffices to predict the partitioning at or around physiological pH. However, at extreme pH values, where ionic species are predominant, more elaborate models provide a better prediction of the n-octanol/water distribution coefficient, especially for amino acid analogues. Finally, the results also show that these formalisms are better suited to reproduce the experimental pH-dependent distribution curves of log D for both acidic and basic compounds as well as for amino acid analogues.

Orthotopic mouse models for the preclinical and translational study of targeted therapies against metastatic human thyroid carcinoma with BRAFV600E or wild-type BRAF

PubMed Central

Antonello, ZA; Nucera, C

2015-01-01

Molecular signature of advanced and metastatic thyroid carcinoma involves deregulation of multiple fundamental pathways activated in the tumor microenvironment. They include BRAFV600E and AKT that affect tumor initiation, progression and metastasis. Human thyroid cancer orthotopic mouse models are based on human cell lines that generally harbor genetic alterations found in human thyroid cancers. They can reproduce in vivo and in situ (into the thyroid) many features of aggressive and refractory human advanced thyroid carcinomas, including local invasion and metastasis. Humanized orthotopic mouse models seem to be ideal and commonly used for preclinical and translational studies of compounds and therapies not only because they may mimic key aspects of human diseases (e.g. metastasis), but also for their reproducibility. In addition, they might provide the possibility to evaluate systemic effects of treatments. So far, human thyroid cancer in vivo models were mainly used to test single compounds, non selective and selective. Despite the greater antitumor activity and lower toxicity obtained with different selective drugs in respect to non-selective ones, most of them are only able to delay disease progression, which ultimately could restart with similar aggressive behavior. Aggressive thyroid tumors (for example, anaplastic or poorly differentiated thyroid carcinoma) carry several complex genetic alterations that are likely cooperating to promote disease progression and might confer resistance to single-compound approaches. Orthotopic models of human thyroid cancer also hold the potential to be good models for testing novel combinatorial therapies. In this article, we will summarize results on preclinical testing of selective and nonselective single compounds in orthotopic mouse models based on validated human thyroid cancer cell lines harboring the BRAFV600E mutation or with wild-type BRAF. Furthermore, we will discuss the potential use of this model also for combinatorial approaches, which are expected to take place in the upcoming human thyroid cancer basic and clinical research. PMID:24362526

A multicore compound glass optical fiber for neutron imaging

NASA Astrophysics Data System (ADS)

Moore, Michael; Zhang, Xiaodong; Feng, Xian; Brambilla, Gilberto; Hayward, Jason

2017-04-01

Optical fibers have been successfully utilized for point sensors targeting physical quantities (stress, strain, rotation, acceleration), chemical compounds (humidity, oil, nitrates, alcohols, DNA) or radiation fields (X-rays, β particles, γ-rays). Similarly, bundles of fibers have been extremely successful in imaging visible wavelengths for medical endoscopy and industrial boroscopy. This work presents the progress in the fabrication and experimental evaluation of multicore fiber as neutron scattering instrumentation designed to detect and image neutrons with micron level spatial resolution.

Aromaticity and Antiaromaticity in Zintl Clusters

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

Sun, Zhong -Ming; Liu, Chao; Popov, Ivan Aleksandrovich

Originally, the concepts of aromaticity and antiaromaticity were introduced to explain the stability and reactivity of unsaturated organic compounds. Since then, they have been extended to other species with delocalized electrons including various saturated systems, organometallic compounds, and even inorganic clusters and molecules. In this study, we focus on the most recent progress of using these concepts to guide experimental synthesis and rationalize geometrical and electronic structures of a particular family of polyanions composed of Group 14 and 15 elements, namely Zintl clusters.

Discovery and structure-activity relationships of a series of pyroglutamic acid amide antagonists of the P2X7 receptor.

PubMed

Abdi, Muna H; Beswick, Paul J; Billinton, Andy; Chambers, Laura J; Charlton, Andrew; Collins, Sue D; Collis, Katharine L; Dean, David K; Fonfria, Elena; Gleave, Robert J; Lejeune, Clarisse L; Livermore, David G; Medhurst, Stephen J; Michel, Anton D; Moses, Andrew P; Page, Lee; Patel, Sadhana; Roman, Shilina A; Senger, Stefan; Slingsby, Brian; Steadman, Jon G A; Stevens, Alexander J; Walter, Daryl S

2010-09-01

A computational lead-hopping exercise identified compound 4 as a structurally distinct P2X(7) receptor antagonist. Structure-activity relationships (SAR) of a series of pyroglutamic acid amide analogues of 4 were investigated and compound 31 was identified as a potent P2X(7) antagonist with excellent in vivo activity in animal models of pain, and a profile suitable for progression to clinical studies. Copyright 2010 Elsevier Ltd. All rights reserved.

Aromaticity and Antiaromaticity in Zintl Clusters

DOE PAGES

Sun, Zhong -Ming; Liu, Chao; Popov, Ivan Aleksandrovich; ...

2018-05-18

Originally, the concepts of aromaticity and antiaromaticity were introduced to explain the stability and reactivity of unsaturated organic compounds. Since then, they have been extended to other species with delocalized electrons including various saturated systems, organometallic compounds, and even inorganic clusters and molecules. In this study, we focus on the most recent progress of using these concepts to guide experimental synthesis and rationalize geometrical and electronic structures of a particular family of polyanions composed of Group 14 and 15 elements, namely Zintl clusters.

75 FR 72963 - Approval and Promulgation of Air Quality Implementation Plans; Maryland; Control of Volatile...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-29

... Promulgation of Air Quality Implementation Plans; Maryland; Control of Volatile Organic Compound Emissions From Industrial Solvent Cleaning Operations; Withdrawal of Direct Final Rule AGENCY: Environmental Protection... withdrawing the direct final rule to approve revisions to Maryland's State Implementation Plan (SIP). This SIP...

Final Approval of California Air Plan Revision; Antelope Valley Air Quality Management District; VOCs From Motor Vehicle Assembly Coating Operations

EPA Pesticide Factsheets

EPA is taking final action to approve a revision to the Antelope Valley Air Quality Management District (AVAQMD) portion of the California SIP concerning the emissions of volatile organic compounds (VOCs) from motor vehicle assembly coating operations.

Olfactometric determination of the most potent odor-active compounds in salmon muscle (Salmo salar) smoked by using four smoke generation techniques.

PubMed

Varlet, Vincent; Serot, Thierry; Cardinal, Mireille; Knockaert, Camille; Prost, Carole

2007-05-30

The volatile compounds of salmon fillets smoked according to four smoked generation techniques (smoldering, thermostated plates, friction, and liquid smoke) were investigated. The main odor-active compounds were identified by gas chromatography coupled with olfactometry and mass spectrometry. Only the odorant volatile compounds detected by at least six judges (out of eight) were identified as potent odorants. Phenolic compounds and guaiacol derivatives were the most detected compounds in the olfactometric profile whatever the smoking process and could constitute the smoky odorant skeleton of these products. They were recovered in the aromatic extracts of salmon smoked by smoldering and by friction, which were characterized by 18 and 25 odor-active compounds, respectively. Furannic compounds were more detected in products smoked with thermostated plates characterized by 26 odorants compounds. Finally, the 27 odorants of products treated with liquid smoke were significantly different from the three others techniques applying wood pyrolysis because pyridine derivatives and lipid oxidation products were perceived in the aroma profile.

Recovering metabolic pathways via optimization.

PubMed

Beasley, John E; Planes, Francisco J

2007-01-01

A metabolic pathway is a coherent set of enzyme catalysed biochemical reactions by which a living organism transforms an initial (source) compound into a final (target) compound. Some of the different metabolic pathways adopted within organisms have been experimentally determined. In this paper, we show that a number of experimentally determined metabolic pathways can be recovered by a mathematical optimization model.

Trapped intermediates in crystals of the FMN-dependent oxidase PhzG provide insight into the final steps of phenazine biosynthesis

USDA-ARS?s Scientific Manuscript database

Phenazine compounds produced by certain species of bacteria have antibiotic activity against a wide range of bacterial and fungal pathogens including many that cause important root diseases of plants. The antibiotic activity of these compounds has long been known but the mechanism of synthesis is po...

Osthole induces apoptosis, suppresses cell-cycle progression and proliferation of cancer cells.

PubMed

Jarząb, Agata; Grabarska, Aneta; Kiełbus, Michał; Jeleniewicz, Witold; Dmoszyńska-Graniczka, Magdalena; Skalicka-Woźniak, Krystyna; Sieniawska, Elwira; Polberg, Krzysztof; Stepulak, Andrzej

2014-11-01

The aim of the present study was to determine the effects of osthole on cell proliferation and viability, cell-cycle progression and induction of apoptosis in human laryngeal cancer RK33 and human medulloblastoma TE671 cell lines. Cell viability was measured by means of the MTT method and cell proliferation by the 5-bromo-2-deoxyuridine (BrdU) incorporation assay. Cell-cycle progression was determined by flow cytometry, and induction of apoptosis by release of oligonucleosomes to the cytosol. The gene expression was estimated by a quantitative polymerase chain reaction (qPCR) method. High-performance counter-current chromatography (HPCCC) was applied for isolation of osthole from fruits of Mutellina purpurea. Osthole decreased proliferation and cell viability of cancer cells in a dose-dependent manner. The tested compound induced apoptosis, increased the cell numbers in G1 and decreased cell number in S/G2 phases of the cell cycle, differentially regulating CDKN1A and TP53 gene expression depending on cancer cell type. Osthole could be considered as a potential compound for cancer therapy and chemoprevention. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Isothiocyanates Are Promising Compounds against Oxidative Stress, Neuroinflammation and Cell Death that May Benefit Neurodegeneration in Parkinson’s Disease

PubMed Central

Sita, Giulia; Hrelia, Patrizia; Tarozzi, Andrea; Morroni, Fabiana

2016-01-01

Parkinson’s disease (PD) is recognized as the second most common neurodegenerative disorder and is characterized by a slow and progressive degeneration of dopaminergic neurons in the substantia nigra. Despite intensive research, the mechanisms involved in neuronal loss are not completely understood yet; however, misfolded proteins, oxidative stress, excitotoxicity and inflammation play a pivotal role in the progression of the pathology. Neuroinflammation may have a greater function in PD pathogenesis than initially believed, taking part in the cascade of events that leads to neuronal death. To date, no efficient therapy, able to arrest or slow down PD, is available. In this context, the need to find novel strategies to counteract neurodegenerative progression by influencing diseases’ pathogenesis is becoming increasingly clear. Isothiocyanates (ITCs) have already shown interesting properties in detoxification, inflammation, apoptosis and cell cycle regulation through the induction of phase I and phase II enzyme systems. Moreover, ITCs may be able to modulate several key points in oxidative and inflammatory evolution. In view of these considerations, the aim of the present review is to describe ITCs as pleiotropic compounds capable of preventing and modulating the evolution of PD. PMID:27598127

Optimization of the solvent-based dissolution method to sample volatile organic compound vapors for compound-specific isotope analysis.

PubMed

Bouchard, Daniel; Wanner, Philipp; Luo, Hong; McLoughlin, Patrick W; Henderson, James K; Pirkle, Robert J; Hunkeler, Daniel

2017-10-20

The methodology of the solvent-based dissolution method used to sample gas phase volatile organic compounds (VOC) for compound-specific isotope analysis (CSIA) was optimized to lower the method detection limits for TCE and benzene. The sampling methodology previously evaluated by [1] consists in pulling the air through a solvent to dissolve and accumulate the gaseous VOC. After the sampling process, the solvent can then be treated similarly as groundwater samples to perform routine CSIA by diluting an aliquot of the solvent into water to reach the required concentration of the targeted contaminant. Among solvents tested, tetraethylene glycol dimethyl ether (TGDE) showed the best aptitude for the method. TGDE has a great affinity with TCE and benzene, hence efficiently dissolving the compounds during their transition through the solvent. The method detection limit for TCE (5±1μg/m 3 ) and benzene (1.7±0.5μg/m 3 ) is lower when using TGDE compared to methanol, which was previously used (385μg/m 3 for TCE and 130μg/m 3 for benzene) [2]. The method detection limit refers to the minimal gas phase concentration in ambient air required to load sufficient VOC mass into TGDE to perform δ 13 C analysis. Due to a different analytical procedure, the method detection limit associated with δ 37 Cl analysis was found to be 156±6μg/m 3 for TCE. Furthermore, the experimental results validated the relationship between the gas phase TCE and the progressive accumulation of dissolved TCE in the solvent during the sampling process. Accordingly, based on the air-solvent partitioning coefficient, the sampling methodology (e.g. sampling rate, sampling duration, amount of solvent) and the final TCE concentration in the solvent, the concentration of TCE in the gas phase prevailing during the sampling event can be determined. Moreover, the possibility to analyse for TCE concentration in the solvent after sampling (or other targeted VOCs) allows the field deployment of the sampling method without the need to determine the initial gas phase TCE concentration. The simplified field deployment approach of the solvent-based dissolution method combined with the conventional analytical procedure used for groundwater samples substantially facilitates the application of CSIA to gas phase studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Improvement of the Pharmacokinetics and In Vivo Antibacterial Efficacy of a Novel Type IIa Topoisomerase Inhibitor by Formulation in Liposomes

PubMed Central

Newman, Joseph; Goteti, Kosalaram; Beaudoin, Marie-Eve; Harrison, Rane; Hopkins, Sussie; Agrawal, Nikunj; Rivin, Olga

2013-01-01

Several useful properties of liposome-based formulations of various existing antibacterial drugs have been reported. These properties include lower MICs, improved pharmacokinetics, lower toxicity, selective distribution to infected tissues, and enhanced in vivo efficacy. Here we report in vivo studies of a liposomal formulation of a member of a novel class of antibacterial type II topoisomerase inhibitors, others of which have progressed to early phases of clinical trials. The free (i.e., nonliposomal) compound has broad-spectrum MICs but suboptimal pharmacokinetics in rats and mice, characterized by a high volume of distribution and rapid clearance. The liposomal formulation of the compound had essentially unchanged MICs but greatly reduced volume of distribution and clearance in rats and mice. In an in vivo mouse model of Staphylococcus aureus infection of one thigh, the liposomal compound localized preferentially to the infected thigh, whereas the free compound showed no preference for the infected versus the uninfected thigh. Most importantly, the liposomal compound had enhanced efficacy at clearing the infection compared with the free compound. Delivery of this class of compounds as liposomal formulations may offer clinical advantages compared with free compounds. PMID:23877679

Integration Of 3D Geographic Information System (GIS) For Effective Waste Management Practice

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

Rood, G.J.; Hecox, G.R.

2006-07-01

Soil remediation in response to the presence of residual radioactivity resulting from past MED/AEC activities is currently in progress under the Formerly Utilized Sites Remedial Action Program near the St. Louis, MO airport. During GY05, approximately 92,000 cubic meters (120,000 cubic yards) of radioactive soil was excavated, packaged and transported via rail for disposal at U.S. Ecology or Envirocare of Utah, LLC. To facilitate the management of excavation/transportation/disposal activities, a 3D GIS was developed for the site that was used to estimate the in-situ radionuclide activities, activities in excavation block areas, and shipping activities using a sum-of ratio (SOR) methodmore » for combining various radionuclide compounds into applicable transportation and disposal SOR values. The 3D GIS was developed starting with the SOR values for the approximately 900 samples from 90 borings. These values were processed into a three-dimensional (3D) point grid using kriging with nominal grid spacing of 1.5 by 1.5 meter horizontal by 0.3 meter vertical. The final grid, clipped to the area and soil interval above the planned base of excavation, consisted of 210,000 individual points. Standard GIS volumetric and spatial join procedures were used to calculate the volume of soil represented by each grid point, the base of excavation, depth below ground surface, elevation, surface elevation and SOR values for each point in the final grid. To create the maps needed for management, the point grid results were spatially joined to each excavation area in 0.9 meter (3 foot) depth intervals and the average SOR and total volumes were calculations. The final maps were color-coded for easy identification of areas above the specific transportation or disposal criteria. (authors)« less

Chemoprevention of esophageal squamous cell carcinoma

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

Stoner, Gary D.; Wang Lishu; Chen Tong

2007-11-01

Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, andmore » to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC.« less

18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures.

PubMed

Papaevgeniou, Nikoletta; Sakellari, Marianthi; Jha, Sweta; Tavernarakis, Nektarios; Holmberg, Carina I; Gonos, Efstathios S; Chondrogianni, Niki

2016-12-01

Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression. Feeding of wild-type Caenorhabditis elegans with 18α-glycyrrhetinic acid (18α-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasome activation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased Aβ deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18α-GA treatment. This is the first report of the use of 18α-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism. Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation-related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet. Antioxid. Redox Signal. 25, 855-869.

Low temperature hydrothermal oil and associated biological precursors in serpentinites from Mid-Ocean Ridge

NASA Astrophysics Data System (ADS)

Pasini, Valerio; Brunelli, Daniele; Dumas, Paul; Sandt, Christophe; Frederick, Joni; Benzerara, Karim; Bernard, Sylvain; Ménez, Bénédicte

2013-09-01

The origin of light hydrocarbons discovered at serpentinite-hosted mid-ocean hydrothermal fields is generally attributed to the abiogenic reduction of carbon (di)oxide by molecular hydrogen released during the progressive hydration of mantle-derived peridotites. These serpentinization by-products represent a valuable source of carbon and energy and are known to support deep microbial ecosystems unrelated to photosynthesis. In addition, the pool of subsurface organic compounds could also include materials derived from the thermal degradation of biological material. We re-investigate the recently described relics of deep microbial ecosystems hosted in serpentinites of the Mid-Atlantic Ridge (4-6°N) in order to study the ageing and (hydro)thermal degradation of the preserved biomass. An integrated set of high resolution micro-imaging techniques (Scanning Electron Microscopy, High Resolution Transmission Electron Microscopy, Raman and Fourier Transform Infra-Red microspectroscopy, Confocal Laser Scanning Microscopy, and Scanning Transmission X-ray Microscopy at the carbon K-edge) has been applied to map the distribution of the different organic components at the micrometer scale and to characterize their speciation and structure. We show that biologically-derived material, containing aliphatic groups, along with carbonyl and amide functional groups, has experienced hydrothermal degradation and slight aromatization. In addition, aliphatic compounds up to C6-C10 with associated carboxylic functional groups wet the host bastite and the late serpentine veins crosscutting the rock. These compounds represent a light soluble organic fraction expelled after biomass degradation through oxidation and thermal cracking. The detected complex organic matter distribution recalls a typical petroleum system, where fossil organic matter of biological origin maturates, expelling the soluble fraction which then migrates from the source to the reservoir. Ecosystem-hosting serpentinites can thus be seen as source rocks generating a net transfer of hydrocarbons and/or fatty acids issued from oxidative processes and primary cracking reactions, then migrating upward through the serpentine vein network. This finally suggests that deep thermogenic organic compounds of biological origin can be a significant contributor to the organic carbon balance at and far below peridotite-hosted hydrothermal fields.

Influence of biphenyl spacer appended to the flexible phosphonate arms in modulating the dimensionality of the coordination polymers: Synthesis, structural chemistry and magnetic properties

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

Tripuramallu, Bharat Kumar; Das, Samar K., E-mail: skdsc@uohyd.ernet.in

2013-01-15

Two new compounds [Co (2,2 Prime -bipy) (H{sub 2}dbp)]{sub n} (1) and [Ni (2,2 Prime -bipy){sub 2}(H{sub 2}dbp)(H{sub 2}O)]{center_dot}H{sub 2}O (2) based on the flexible ligand 4,4 Prime -dimethylenebiphenyldiphosphonic acid (H{sub 4}dbp) with 2,2 Prime -bipyridine as secondary ligand have been synthesized under hydrothermal conditions. Both the compounds are well characterized by routine elemental analysis, IR, electronic spectroscopies, thermogravimetric analysis and finally by single crystal X-ray diffraction analysis. Compound 1 is a 1D extended coordination polymer and 2 is a discrete molecular compound. A comparative study between the geometries of H{sub 4}dbp ligand (in compounds 1 and 2, present study)more » and p-xylylenediphosphonic acid (H{sub 4}pxp) ligand (in previously reported compounds [Cu(2,2 Prime -bipy)(H{sub 2}pxp)]{center_dot}nH{sub 2}O (1A) and Ni(2,2 Prime -bipy){sub 2}H{sub 4}pxp]{sub n}[H{sub 2}pxp]{sub n} (2A), see text) demonstrate the effect of the twisting in the benzene rings in changing higher dimensional H{sub x}pxp (x refers to number of protonated hydroxyl groups) compounds to lower dimensional H{sub x}dbp compounds. The eight membered Co-dimer rings formed in compound 1 represents the simple and isolated Co-dimer, exhibiting weak antiferromagnetic exchange between metal centers through OPO bridges. - Graphical abstract: Two new compounds based on the dimethylenebiphenyldiphosphonic acid have been synthesized. The effect of twisting of benzene rings in the biphenyl spacer containing multidentate ligands alters dimensionality of final compounds. Highlights: Black-Right-Pointing-Pointer Cobalt containing coordination polymer and a nickel discrete compound have been synthesized. Black-Right-Pointing-Pointer Flexible ligand 4,4'-dimethylenebiphenyldiphosphonic acid has been employed. Black-Right-Pointing-Pointer Co(II) and Ni(II) ions are square pyramidal and octahedral respectively. Black-Right-Pointing-Pointer The effect of the twisting in the benzene rings in the associated ligand has been demonstrated.« less

A convenient route to [68Ga]Ga-MAA for use as a particulate PET perfusion tracer.

PubMed

Mathias, Carla J; Green, Mark A

2008-12-01

A convenient method is described for compounding [(68)Ga]Ga-MAA (MAA=macroaggregated human serum albumin) with the eluate of a commercially available TiO(2)-based (68)Ge/(68)Ga generator. The final [(68)Ga]Ga-MAA product was obtained with an 81.6+/-5.3% decay-corrected radiochemical yield and a radiochemical purity of 99.8+/-0.1% (n=5). Microscopic examination showed the [(68)Ga]Ga-MAA product to remain within the original particle size range. The entire procedure, from generator elution to delivery of the final [(68)Ga]Ga-MAA suspension, could be completed in 25 min. Only 4.4+/-0.9% of the total (68)Ge breakthrough remaining associated with the final [(68)Ga]Ga-MAA product. The procedure allows reasonably convenient preparation of [(68)Ga]Ga-MAA in a fashion that can be readily adapted to sterile product compounding for human use.

Amorphous cellulose gel as a fat substitute in fermented sausages.

PubMed

Campagnol, Paulo Cezar Bastianello; dos Santos, Bibiana Alves; Wagner, Roger; Terra, Nelcindo Nascimento; Rodrigues Pollonio, Marise Aparecida

2012-01-01

Fermented sausages were produced with 25%, 50%, 75% or 100% of their pork back fat content replaced by amorphous cellulose gel. The sausage production was monitored with physical, chemical and microbiological analyses. The final products were submitted to a consumer study, and the volatile compounds of the final products were extracted by solid-phase microextraction and analyzed by GC/MS. The reformulated fermented sausages had significant reductions in fat and cholesterol, and the volatile compounds derived from lipid oxidation were also reduced in the final products. These results suggest that the substitution of up to 50% of the pork back fat content by amorphous cellulose gel can be accomplished without a loss of product quality, enabling the production of fermented sausages with the levels of fat and cholesterol decreased by approximately 45% and 15%, respectively. Copyright © 2011 Elsevier Ltd. All rights reserved.

Iron Promotes the Toxicity of Amyloid β Peptide by Impeding Its Ordered Aggregation*

PubMed Central

Liu, Beinan; Moloney, Aileen; Meehan, Sarah; Morris, Kyle; Thomas, Sally E.; Serpell, Louise C.; Hider, Robert; Marciniak, Stefan J.; Lomas, David A.; Crowther, Damian C.

2011-01-01

We have previously shown that overexpressing subunits of the iron-binding protein ferritin can rescue the toxicity of the amyloid β (Aβ) peptide in our Drosophila model system. These data point to an important pathogenic role for iron in Alzheimer disease. In this study, we have used an iron-selective chelating compound and RNAi-mediated knockdown of endogenous ferritin to further manipulate iron in the brain. We confirm that chelation of iron protects the fly from the harmful effects of Aβ. To understand the pathogenic mechanisms, we have used biophysical techniques to see how iron affects Aβ aggregation. We find that iron slows the progression of the Aβ peptide from an unstructured conformation to the ordered cross-β fibrils that are characteristic of amyloid. Finally, using mammalian cell culture systems, we have shown that iron specifically enhances Aβ toxicity but only if the metal is present throughout the aggregation process. These data support the hypothesis that iron delays the formation of well ordered aggregates of Aβ and so promotes its toxicity in Alzheimer disease. PMID:21147772

Iron promotes the toxicity of amyloid beta peptide by impeding its ordered aggregation.

PubMed

Liu, Beinan; Moloney, Aileen; Meehan, Sarah; Morris, Kyle; Thomas, Sally E; Serpell, Louise C; Hider, Robert; Marciniak, Stefan J; Lomas, David A; Crowther, Damian C

2011-02-11

We have previously shown that overexpressing subunits of the iron-binding protein ferritin can rescue the toxicity of the amyloid β (Aβ) peptide in our Drosophila model system. These data point to an important pathogenic role for iron in Alzheimer disease. In this study, we have used an iron-selective chelating compound and RNAi-mediated knockdown of endogenous ferritin to further manipulate iron in the brain. We confirm that chelation of iron protects the fly from the harmful effects of Aβ. To understand the pathogenic mechanisms, we have used biophysical techniques to see how iron affects Aβ aggregation. We find that iron slows the progression of the Aβ peptide from an unstructured conformation to the ordered cross-β fibrils that are characteristic of amyloid. Finally, using mammalian cell culture systems, we have shown that iron specifically enhances Aβ toxicity but only if the metal is present throughout the aggregation process. These data support the hypothesis that iron delays the formation of well ordered aggregates of Aβ and so promotes its toxicity in Alzheimer disease.

Syk inhibitors.

PubMed

Chihara, Kazuyasu; Kimura, Yukihiro; Honjo, Chisato; Takeuchi, Kenji; Sada, Kiyonao

2013-01-01

Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in University of Fukui in 1991. Syk is most highly expressed by haemopoietic cells and known to play crucial roles in the signal transduction through various immunoreceptors of the adaptive immune response. However, recent reports demonstrate that Syk also mediates other biological functions, such as innate immune response, osteoclast maturation, platelet activation and cellular adhesion. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Because of its critical roles on the cellular functions, the development of Syk inhibitors for clinical use has been desired. Although many candidate compounds were produced, none of them had progressed to clinical trials. However, novel Syk inhibitors were finally developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure and function of Syk, and then the novel Syk inhibitors and their current status. In addition, we will introduce our research focused on the functions of Syk on Dectin-1-mediated mast cell activation.

Wide-Field InfraRed Survey Telescope (WFIRST) Slitless Spectrometer: Design, Prototype, and Results

NASA Technical Reports Server (NTRS)

Gong, Qian; Content, David; Dominguez, Margaret; Emmett, Thomas; Griesmann, Ulf; Hagopian, John; Kruk, Jeffrey; Marx, Catherine; Pasquale, Bert; Wallace, Thomas;

Imaging in Central Nervous System Drug Discovery.

PubMed

Gunn, Roger N; Rabiner, Eugenii A

2017-01-01

The discovery and development of central nervous system (CNS) drugs is an extremely challenging process requiring large resources, timelines, and associated costs. The high risk of failure leads to high levels of risk. Over the past couple of decades PET imaging has become a central component of the CNS drug-development process, enabling decision-making in phase I studies, where early discharge of risk provides increased confidence to progress a candidate to more costly later phase testing at the right dose level or alternatively to kill a compound through failure to meet key criteria. The so called "3 pillars" of drug survival, namely; tissue exposure, target engagement, and pharmacologic activity, are particularly well suited for evaluation by PET imaging. This review introduces the process of CNS drug development before considering how PET imaging of the "3 pillars" has advanced to provide valuable tools for decision-making on the critical path of CNS drug development. Finally, we review the advances in PET science of biomarker development and analysis that enable sophisticated drug-development studies in man. Copyright © 2017 Elsevier Inc. All rights reserved.

Atrogin-1 Deficiency Leads to Myopathy and Heart Failure in Zebrafish.

PubMed

Bühler, Anja; Kustermann, Monika; Bummer, Tiziana; Rottbauer, Wolfgang; Sandri, Marco; Just, Steffen

2016-01-30

Orchestrated protein synthesis and degradation is fundamental for proper cell function. In muscle, impairment of proteostasis often leads to severe cellular defects finally interfering with contractile function. Here, we analyze for the first time the role of Atrogin-1, a muscle-specific E3 ubiquitin ligase known to be involved in the regulation of protein degradation via the ubiquitin proteasome and the autophagy/lysosome systems, in the in vivo model system zebrafish (Danio rerio). We found that targeted inactivation of zebrafish Atrogin-1 leads to progressive impairment of heart and skeletal muscle function and disruption of muscle structure without affecting early cardiogenesis and skeletal muscle development. Autophagy is severely impaired in Atrogin-1-deficient zebrafish embryos resulting in the disturbance of the cytoarchitecture of cardiomyocytes and skeletal muscle cells. These observations are consistent with molecular and ultrastructural findings in an Atrogin-1 knockout mouse and demonstrate that the zebrafish is a suitable vertebrate model to study the molecular mechanisms of Atrogin-1-mediated autophagic muscle pathologies and to screen for novel therapeutically active substances in high-throughput in vivo small compound screens (SCS).

Potential phytocompounds for developing breast cancer therapeutics: Nature's healing touch.

PubMed

Iqbal, Javed; Abbasi, Banzeer Ahsan; Batool, Riffat; Mahmood, Tariq; Ali, Barkat; Khalil, Ali Talha; Kanwal, Sobia; Shah, Sayed Afzal; Ahmad, Riaz

2018-05-15

Breast cancer (BC) is a devastating disease in female around the world causing significant health care burden in both developed and developing countries. In many cases BC has shown resistance to chemotherapy, radiation and hormonal therapy. Development of new, cost effective, affordable treatment method is the need of hour. Chemical compounds isolated from plants are often biologically active and is attracting the attention of scientific community. Different in vitro and in vivo studies have shown a potential role in reducing the risk of cancer metastasis. Large number of phytochemicals are considered to regulate several molecular and metabolic processes like cell cycle regulation, apoptosis activation, angiogenesis and metastatic suppression that can hinders cancer progression. An extensive review of literature has been conducted to underline the key phytochemicals and their mechanism of action. This review article has discussed in detail the regulatory roles of phytochemicals, their analogs and nanoformulations and the probability of using phytochemicals in therapeutic management of BC. Finally, current limitations, challenges and future perspectives of these phytochemicals are also critically discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of final baking technologies in partially baked frozen gluten-free bread quality.

PubMed

Aguilar, Núria; Albanell, Elena; Miñarro, Begoña; Gallardo, Joan; Capellas, Marta

2015-03-01

The effect of final baking in convection oven (FBC), microwave oven (FBM), and microwave oven with susceptor packaging material (FBMS) on partially baked (PB) frozen gluten-free bread characteristics was investigated. Specific volume and crust color of loaves were measured at day 0. Bread moisture, water activity, and crumb and crust texture (at 15, 45, and 90 min after baking) were analyzed at day 0 and after 28 d of frozen storage (-18 °C). Volatile compounds from breads baked in convection oven or microwave oven with susceptor packaging material were also evaluated. Bread finally baked in convection oven or in microwave oven with susceptor packaging increased crust browning. Crumb and roll hardness increased with time after final baking (measured at 15, 45, 90 min) and after 28 d of frozen storage. Bread finally baked in microwave oven was the hardest, due to high water losses. At day 0, bread finally baked in convection oven had softer crumb than bread finally baked in microwave oven with susceptor packaging but, after 28 d of frozen storage, there were no differences between them. Moreover, FBC and FBMS rendered gluten-free breads that could not be distinguished in a triangular test and had the same volatile compounds profile. In conclusion, FBMS could be an alternative to FBC. © 2015 Institute of Food Technologists®

Propolis Diterpenes as a Remarkable Bio-Source for Drug Discovery Development: A Review.

PubMed

Aminimoghadamfarouj, Noushin; Nematollahi, Alireza

2017-06-17

Propolis is one of the complex, but valuable, bio-sources for discovering therapeutic compounds. Diterpenes are organic compounds composed of four isoprene units and are known for their biological and pharmacological characteristics, such as antibacterial, anticancer, and anti-inflammatory activities. Recently, advancements have been made in the development of antibacterial and anticancer leads from propolis-isolated diterpenes, and scrutiny of these compounds is being pursued. Thus, this review covers the progress in this arena, with a focus on the chemistry and biological activities of propolis diterpenes. It is anticipated that important information, in a comprehensive and concise manner, will be delivered here for better understanding of natural product drug discovery research.

Propolis Diterpenes as a Remarkable Bio-Source for Drug Discovery Development: A Review

PubMed Central

Aminimoghadamfarouj, Noushin; Nematollahi, Alireza

2017-01-01

Propolis is one of the complex, but valuable, bio-sources for discovering therapeutic compounds. Diterpenes are organic compounds composed of four isoprene units and are known for their biological and pharmacological characteristics, such as antibacterial, anticancer, and anti-inflammatory activities. Recently, advancements have been made in the development of antibacterial and anticancer leads from propolis-isolated diterpenes, and scrutiny of these compounds is being pursued. Thus, this review covers the progress in this arena, with a focus on the chemistry and biological activities of propolis diterpenes. It is anticipated that important information, in a comprehensive and concise manner, will be delivered here for better understanding of natural product drug discovery research. PMID:28629133

29 CFR 97.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-07-01

... limited to: (1) Final performance or progress report. (2) Financial Status Report (SF 269) or Outlay Report and Request for Reimbursement for Construction Programs (SF-271) (as applicable.) (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5) Federally...

36 CFR 1207.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-07-01

... limited to: (1) Final performance or progress report. (2) Financial Status Report (SF 269) or Outlay Report and Request for Reimbursement for Construction Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5) Federally...

Micro-ion Traps for Detection of (Pre)-Biotic Organic Compounds on Comets

NASA Technical Reports Server (NTRS)

vanAmerom, Friso H. W.; Chaudhary, A.; Short, R. T.; Brinkerhoff, William; Glavin, Daniel; Mahaffy, Paul R.; Roman, Patrick A.

2013-01-01

Comets are currently believed to be a mixture of interstellar and nebular material. Many of the volatiles in comets are attributed to interstellar chemistry, because the same species of carbonaceous compounds are also observed in ices in interstellar molecular (ISM) clouds. Comets are thus likely to be a relatively pristine reservoir of primitive material and carbonaceous compounds in our solar system. They could be a major contributor to the delivery of prebiotic organic compounds, from which life emerged through impacts on early Earth. Mass spectrometers are very powerful tools to identify unknown chemicals, and much progress bas been made in miniaturizing mas spectrometers for space applications. Most miniatu rized mass spectrometers developed to date, however, are still relatively large, power hungry, complicated to assemble, and would have significant impact on space flight vehicle total payload and resource allocations.

Metastasis: recent discoveries and novel perioperative treatment strategies with particular interest in the hemostatic compound desmopressin.

PubMed

Alonso, D F; Ripoll, G V; Garona, J; Iannucci, N B; Gomez, D E

2011-11-01

Metastatic disease is responsible for most of cancer lethality. A main obstacle for therapy of advanced cancers is that the outcome of metastasis depends on a complex interplay between malignant and host cells. The perioperative period represents an underutilized window of opportunity for cancer treatment where tumor-host interactions can be modulated, reducing the risk of local recurrences and distant metastases. Blood-saving agents are attractive compounds to be administered during tumor surgery. Desmopressin (DDAVP) is a safe and convenient hemostatic peptide with proved antimetastastic properties in experimental models and veterinary clinical trials. The compound seems to induce a dual angiostatic and antimetastatic effect, breaking the cooperative function of cancer cells and endothelial cells during residual tumor progression. DDAVP is therefore an interesting lead compound to develop novel synthetic peptide analogs with enhanced antitumor properties.

78 FR 63875 - Progress Reports Rules Revision

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

... Reports Rules Revision AGENCY: Bureau of Prisons, Justice. ACTION: Final rule. SUMMARY: In this document, the Bureau of Prisons (Bureau) removes from regulations and/or modifies two types of progress reports: transfer reports and triennial reports. DATES: This rule is effective on November 25, 2013. FOR FURTHER...

Next Generation Attenuation Relationships for the Eastern United States (NGA-East)

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

Mahin, Stephen; Bozorgnia, Yousef

2016-04-11

This is a progress report to DOE for project Next Generation Attenuation for Central & Eastern US (NGA-East).This progress report consists of numerous monthly progress segments starting June 1, 2010 until December 31, 2015. Please note: the December 2015 progress report was issued in January 2016 due to the final university financial reporting at the end of this project. For each month, there is a technical progress list, and an update on the financial progress of the project. As you know, this project is jointly funded by the DOE, US Nuclear Regulatory Commission (NRC) and Electric Power Research Institute (EPRI).more » Thus, each segment includes financial progress for these three funding agencies.« less

Extreme Performance Scalable Operating Systems Final Progress Report (July 1, 2008 - October 31, 2011)

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

Malony, Allen D; Shende, Sameer

This is the final progress report for the FastOS (Phase 2) (FastOS-2) project with Argonne National Laboratory and the University of Oregon (UO). The project started at UO on July 1, 2008 and ran until April 30, 2010, at which time a six-month no-cost extension began. The FastOS-2 work at UO delivered excellent results in all research work areas: * scalable parallel monitoring * kernel-level performance measurement * parallel I/0 system measurement * large-scale and hybrid application performance measurement * onlne scalable performance data reduction and analysis * binary instrumentation

Partial Return Yoke for MICE Step IV and Final Step

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

Witte, Holger; Plate, Stephen; Berg, J.Scott

2015-06-01

This paper reports on the progress of the design and construction of a retro-fitted return yoke for the international Muon Ionization Cooling Experiment (MICE). MICE is a proof-of-principle experiment aiming to demonstrate ionization cooling experimentally. In earlier studies we outlined how a partial return yoke can be used to mitigate stray magnetic field in the experimental hall; we report on the progress of the construction of the partial return yoke for MICE Step IV. We also discuss an extension of the Partial Return Yoke for the final step of MICE; we show simulation results of the expected performance.

Partial return yoke for MICE step IV and final step

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

Witte, H.; Plate, S.; Berg, J. S.

2015-05-03

This paper reports on the progress of the design and construction of a retro-fitted return yoke for the international Muon Ionization Cooling Experiment (MICE). MICE is a proof-of-principle experiment aiming to demonstrate ionization cooling experimentally. In earlier studies we outlined how a partial return yoke can be used to mitigate stray magnetic field in the experimental hall; we report on the progress of the construction of the partial return yoke for MICE Step IV. We also discuss an extension of the Partial Return Yoke for the final step of MICE; we show simulation results of the expected performance.

Method of upgrading oils containing hydroxyaromatic hydrocarbon compounds to highly aromatic gasoline

DOEpatents

Baker, E.G.; Elliott, D.C.

1993-01-19

The present invention is a multi-stepped method of converting an oil which is produced by various biomass and coal conversion processes and contains primarily single and multiple ring hydroxyaromatic hydrocarbon compounds to highly aromatic gasoline. The single and multiple ring hydroxyaromatic hydrocarbon compounds in a raw oil material are first deoxygenated to produce a deoxygenated oil material containing single and multiple ring aromatic compounds. Then, water is removed from the deoxygenated oil material. The next step is distillation to remove the single ring aromatic compounds as gasoline. In the third step, the multiple ring aromatics remaining in the deoxygenated oil material are cracked in the presence of hydrogen to produce a cracked oil material containing single ring aromatic compounds. Finally, the cracked oil material is then distilled to remove the single ring aromatics as gasoline.

Novel ocular antihypertensive compounds in clinical trials

PubMed Central

Chen, June; Runyan, Stephen A; Robinson, Michael R

2011-01-01

Introduction: Glaucoma is a multifactorial disease characterized by progressive optic nerve injury and visual field defects. Elevated intraocular pressure (IOP) is the most widely recognized risk factor for the onset and progression of open-angle glaucoma, and IOP-lowering medications comprise the primary treatment strategy. IOP elevation in glaucoma is associated with diminished or obstructed aqueous humor outflow. Pharmacotherapy reduces IOP by suppressing aqueous inflow and/or increasing aqueous outflow. Purpose: This review focuses on novel non-FDA approved ocular antihypertensive compounds being investigated for IOP reduction in ocular hypertensive and glaucoma patients in active clinical trials within approximately the past 2 years. Methods: The mode of IOP reduction, pharmacology, efficacy, and safety of these new agents were assessed. Relevant drug efficacy and safety trials were identified from searches of various scientific literature databases and clinical trial registries. Compounds with no specified drug class, insufficient background information, reformulations, and fixed-combinations of marketed drugs were not considered. Results: The investigational agents identified comprise those that act on the same targets of established drug classes approved by the FDA (ie, prostaglandin analogs and β-adrenergic blockers) as well as agents belonging to novel drug classes with unique mechanisms of action. Novel targets and compounds evaluated in clinical trials include an actin polymerization inhibitor (ie, latrunculin), Rho-associated protein kinase inhibitors, adenosine receptor analogs, an angiotensin II type 1 receptor antagonist, cannabinoid receptor agonists, and a serotonin receptor antagonist. Conclusion: The clinical value of novel compounds for the treatment of glaucoma will depend ultimately on demonstrating favorable efficacy and benefit-to-risk ratios relative to currently approved prostaglandin analogs and β-blockers and/or having complementary modes of action. PMID:21629573

A comparison of the cytological effects of three hypoxic cell radiosensitizers

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

Spunberg, J.J.; Geard, C.R.; Rutledge-Freeman, M.H.

1982-07-01

Misonidazole has entered Phase III clinical trials as a hypoxic cell radiosensitizer. Neurotoxocity is the major dose-limiting factor and has prompted the development of two further compounds with reduced lipophilicity and shorter half-life in vivo. Aside from the short-term problem of neurotoxicity, other potential long-term consequences should be considered. Such is the purpose of this investigation where the cytological effects of three radiosensitizers upon oxic and hypoxic Chinese hamster V-79 cells have been examined. Two newer compounds, desmethylmisonidazole and Stanford Research compound 2508, were compared with their clinically used predecessor misonidazole. Under aerated conditions, cell killing was increased with SR-2508more » in a concentration and time dependent manner, so as to exceed by more than three times the level produced by the other two drugs at 5 mM for 72 hours.Cell progression into mitosis was also markedly reduced by as much as 1/10,000 of control values. However, as the three compounds induced similar frequencies of sister chromatid exchange (SCE) and chromosome aberration, the enhanced cytotoxic effect of SR-2508 appears to be mediated via an interphase rather than a post-mitotic cell death. Cells were made hypoxic and treated with the three drugs for 4 hr, then mitoses sequentially collected for 16 hr. The three compounds produced similar levels of cell killing, slowing of cell cycle progression, SCE's and chromosome aberrations, with cycle-specific effect on S and G-I phase cells for SCE induction. These results indicate that desmethylmisonidazole and misonidazole have similar cytotoxic and clastogenic properties under oxic and hypoxic conditions. SR-2508 is relatively more toxic to aerated cells and may deserve close clinical observation for toxicity to normal tissues.« less

MBE Growth of Ferromagnetic Metal/Compound Semiconductor Heterostructures for Spintronics

ScienceCinema

Palmstrom, Chris [University of California, Santa Barbara, California, United States

2017-12-09

Electrical transport and spin-dependent transport across ferromagnet/semiconductor contacts is crucial in the realization of spintronic devices. Interfacial reactions, the formation of non-magnetic interlayers, and conductivity mismatch have been attributed to low spin injection efficiency. MBE has been used to grow epitaxial ferromagnetic metal/GA(1-x)AL(x)As heterostructures with the aim of controlling the interfacial structural, electronic, and magnetic properties. In situ, STM, XPS, RHEED and LEED, and ex situ XRD, RBS, TEM, magnetotransport, and magnetic characterization have been used to develop ferromagnetic elemental and metallic compound/compound semiconductor tunneling contacts for spin injection. The efficiency of the spin polarized current injected from the ferromagnetic contact has been determined by measuring the electroluminescence polarization of the light emitted from/GA(1-x)AL(x)As light-emitting diodes as a function of applied magnetic field and temperature. Interfacial reactions during MBE growth and post-growth anneal, as well as the semiconductor device band structure, were found to have a dramatic influence on the measured spin injection, including sign reversal. Lateral spin-transport devices with epitaxial ferromagnetic metal source and drain tunnel barrier contacts have been fabricated with the demonstration of electrical detection and the bias dependence of spin-polarized electron injection and accumulation at the contacts. This talk emphasizes the progress and achievements in the epitaxial growth of a number of ferromagnetic compounds/III-V semiconductor heterostructures and the progress towards spintronic devices.

Glucocorticoids Suppress Renal Cell Carcinoma Progression by Enhancing Na,K-ATPase Beta-1 Subunit Expression

PubMed Central

Huynh, Thu P.; Barwe, Sonali P.; Lee, Seung J.; McSpadden, Ryan; Franco, Omar E.; Hayward, Simon W.; Damoiseaux, Robert; Grubbs, Stephen S.; Petrelli, Nicholas J.; Rajasekaran, Ayyappan K.

2015-01-01

Glucocorticoids are commonly used as palliative or chemotherapeutic clinical agents for treatment of a variety of cancers. Although steroid treatment is beneficial, the mechanisms by which steroids improve outcome in cancer patients are not well understood. Na,K-ATPase beta-subunit isoform 1 (NaK-β1) is a cell-cell adhesion molecule, and its expression is down-regulated in cancer cells undergoing epithelial-to mesenchymal-transition (EMT), a key event associated with cancer progression to metastatic disease. In this study, we performed high-throughput screening to identify small molecules that could up-regulate NaK-β1 expression in cancer cells. Compounds related to the glucocorticoids were identified as drug candidates enhancing NaK-β1 expression. Of these compounds, triamcinolone, dexamethasone, and fluorometholone were validated to increase NaK-β1 expression at the cell surface, enhance cell-cell adhesion, attenuate motility and invasiveness and induce mesenchymal to epithelial like transition of renal cell carcinoma (RCC) cells in vitro. Treatment of NaK-β1 knockdown cells with these drug candidates confirmed that these compounds mediate their effects through up-regulating NaK-β1. Furthermore, we demonstrated that these compounds attenuate tumor growth in subcutaneous RCC xenografts and reduce local invasiveness in orthotopically-implanted tumors. Our results strongly indicate that the addition of glucocorticoids in the treatment of RCC may improve outcome for RCC patients by augmenting NaK-β1 cell-cell adhesion function. PMID:25836370

Electrochemical properties of copper-based compounds with polyanion frameworks

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

Mizuno, Yoshifumi; Hata, Shoma; Suzuki, Kota

The copper-based polyanion compounds Li{sub 6}CuB{sub 4}O{sub 10} and Li{sub 2}CuP{sub 2}O{sub 7} were synthesized using a conventional solid-state reaction, and their electrochemical properties were determined. Li{sub 6}CuB{sub 4}O{sub 10} showed reversible capacity of 340 mA g{sup −1} at the first discharge–charge process, while Li{sub 2}CuP{sub 2}O{sub 7} showed large irreversible capacity and thus low charge capacity. Ex situ X-ray diffraction (XRD) and X-ray absorption near edge structure (XANES) measurements revealed that the electrochemical Li{sup +} intercalation/deintercalation reaction in Li{sub 6}CuB{sub 4}O{sub 10} occurred via reversible Cu{sup 2+}/Cu{sup +} reduction/oxidation reaction. These differences in their discharge/charge mechanisms are discussed basedmore » on the strength of the Cu–O covalency via their inductive effects. - Graphical abstract: Electrochemical properties for Cu-based polyanion compounds were investigated. The electrochemical reaction mechanisms are strongly affected by their Cu–O covalentcy. - Highlights: • Electrochemical properties of Cu-based polyanion compounds were investigated. • The Li{sup +} intercalation/deintercalation reaction progressed in Li{sub 6}CuB{sub 4}O{sub 10}. • The electrochemical displacement reaction progressed in Li{sub 2}CuP{sub 2}O{sub 7}. • The strength of Cu–O covalency affects the reaction mechanism.« less

Indium Lung Disease

PubMed Central

Nakano, Makiko; Omae, Kazuyuki; Takeuchi, Koichiro; Chonan, Tatsuya; Xiao, Yong-long; Harley, Russell A.; Roggli, Victor L.; Hebisawa, Akira; Tallaksen, Robert J.; Trapnell, Bruce C.; Day, Gregory A.; Saito, Rena; Stanton, Marcia L.; Suarthana, Eva; Kreiss, Kathleen

2012-01-01

Background: Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. Methods: To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. Results: Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. Conclusions: Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies. PMID:22207675

7 CFR 3016.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF 269) or Outlay Report and Request for Reimbursement for Construction Programs (SF-271) (as applicable.) (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5) Federally...

Evaluation of a Progressive Failure Analysis Methodology for Laminated Composite Structures

NASA Technical Reports Server (NTRS)

Sleight, David W.; Knight, Norman F., Jr.; Wang, John T.

1997-01-01

A progressive failure analysis methodology has been developed for predicting the nonlinear response and failure of laminated composite structures. The progressive failure analysis uses C plate and shell elements based on classical lamination theory to calculate the in-plane stresses. Several failure criteria, including the maximum strain criterion, Hashin's criterion, and Christensen's criterion, are used to predict the failure mechanisms. The progressive failure analysis model is implemented into a general purpose finite element code and can predict the damage and response of laminated composite structures from initial loading to final failure.

(-)-Gossypol reduces invasiveness in metastatic prostate cancer cells

USDA-ARS?s Scientific Manuscript database

Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. (-)-Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferation and pro-apoptotic effects in various cancer cells. In this study, the differences betwee...

Final report : for the period of December 1999 through November 30, 2000 : Florida Transit Training Program (1999/2000) : Florida Technical Assistance Program (1999/2000)

DOT National Transportation Integrated Search

2000-01-01

The following progress report is intended to highlight the significant activities of the Florida Transit Training Program and Florida Technical Assistant Program. The following progress report is intended to highlight the significant activities of th...

Evaluation of the National Assessment of Educational Progress. Study Reports

ERIC Educational Resources Information Center

Buckendahl, Chad W.; Davis, Susan L.; Plake, Barbara S.; Sireci, Stephen G.; Hambleton, Ronald K.; Zenisky, April L.; Wells, Craig S.

2009-01-01

The "Evaluation of the National Assessment of Educational Progress: Study Reports" describes the special studies that comprised the design of the evaluation. In the Final Report, the authors presented a practical discussion of the evaluation studies to its primary, intended audience, namely policymakers. On this accompanying CD, readers…

10 CFR 600.341 - Monitoring and reporting program and financial performance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... will be taken to address the deviations. (2) A final technical report if the award is for research and... dates for reports. At a minimum, requirements must include: (1) Periodic progress reports (at least... follows: (i) The program portions of the reports must address progress toward achieving program...

10 CFR 600.341 - Monitoring and reporting program and financial performance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... will be taken to address the deviations. (2) A final technical report if the award is for research and... dates for reports. At a minimum, requirements must include: (1) Periodic progress reports (at least... follows: (i) The program portions of the reports must address progress toward achieving program...

10 CFR 600.341 - Monitoring and reporting program and financial performance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... will be taken to address the deviations. (2) A final technical report if the award is for research and... dates for reports. At a minimum, requirements must include: (1) Periodic progress reports (at least... follows: (i) The program portions of the reports must address progress toward achieving program...

10 CFR 600.341 - Monitoring and reporting program and financial performance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... will be taken to address the deviations. (2) A final technical report if the award is for research and... dates for reports. At a minimum, requirements must include: (1) Periodic progress reports (at least... follows: (i) The program portions of the reports must address progress toward achieving program...

Reduced posting and marking of flight progress strips for en route air traffic control : final report.

DOT National Transportation Integrated Search

2000-02-01

The new Display System Replacement (DSR) being implemented in air route traffic control centers (ARTCCs) will allow the data-side controller less room to post Flight Progress Strips (FPSs). We tested a new FPS marking and posting procedure designed t...

Minorities in Higher Education: A Pipeline Problem?

ERIC Educational Resources Information Center

Sethna, Beheruz N.

2011-01-01

This paper uses national data from the American Council on Education (ACE) to study the progress of different ethnic groups through the academic pipeline--stages studied include the Bachelor's, Master's, doctoral, levels, and then progress to the Assistant, Associate, and (full) Professor stages, to full-time administrators and finally to the CEO…

46 CFR 172.245 - Survival conditions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... conditions. A vessel is presumed to survive assumed damage if it meets the following conditions in the final..., and trim must be below the lower edge of an opening through which progressive flooding may take place... inches (50 mm) when the vessel is in the equilibrium position. (e) Progressive flooding. In the design...

46 CFR 172.245 - Survival conditions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... conditions. A vessel is presumed to survive assumed damage if it meets the following conditions in the final..., and trim must be below the lower edge of an opening through which progressive flooding may take place... inches (50 mm) when the vessel is in the equilibrium position. (e) Progressive flooding. In the design...

46 CFR 172.245 - Survival conditions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... conditions. A vessel is presumed to survive assumed damage if it meets the following conditions in the final..., and trim must be below the lower edge of an opening through which progressive flooding may take place... inches (50 mm) when the vessel is in the equilibrium position. (e) Progressive flooding. In the design...

The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders

PubMed Central

Działo, Magdalena; Mierziak, Justyna; Korzun, Urszula; Preisner, Marta; Szopa, Jan; Kulma, Anna

2016-01-01

Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract. PMID:26901191

Chemical Substitution and High Pressure Effects on Superconductors in the LnOBiS$$_2$$ (Ln = La-Nd) System

DOE PAGES

Fang, Yuankan; Wolowiec, Christian T.; Yazici, Duygu; ...

2015-12-14

A large number of compounds which contain BiSmore » $$_2$$ layers exhibit enhanced superconductivity upon electron doping. Much interest and research effort has been focused on BiS$$_2$$-based compounds which provide new opportunities for exploring the nature of superconductivity. Important to the study of BiS2-based superconductors is the relation between structure and superconductivity. By modifying either the superconducting BiS$$_2$$ layers or the blocking layers in these layered compounds, one can effectively tune the lattice parameters, local atomic environment, electronic structure, and other physical properties of these materials. In this article, we will review some of the recent progress on research of the effects of chemical substitution in BiS$$_2$$-based compounds, with special attention given to the compounds in the LnOBiSS$$_2$$ (Ln = La-Nd) system. Strategies which are reported to be essential in optimizing superconductivity of these materials will also be discussed.« less

Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules.

PubMed

Dave, Vivek S; Gupta, Deepak; Yu, Monica; Nguyen, Phuong; Varghese Gupta, Sheeba

2017-02-01

The Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability. Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/hybridization of one or more traditional approaches to improve drug permeability. While some of these approaches have been extremely successful, i.e. drug products utilizing the approach have progressed through the USFDA approval for marketing; others require further investigation to be applicable. This article discusses the commonly studied approaches for improving the permeability of BCS Class III compounds.

The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders.

PubMed

Działo, Magdalena; Mierziak, Justyna; Korzun, Urszula; Preisner, Marta; Szopa, Jan; Kulma, Anna

2016-02-18

Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract.

Progress in linear optics, non-linear optics and surface alignment of liquid crystals

NASA Astrophysics Data System (ADS)

Ong, H. L.; Meyer, R. B.; Hurd, A. J.; Karn, A. J.; Arakelian, S. M.; Shen, Y. R.; Sanda, P. N.; Dove, D. B.; Jansen, S. A.; Hoffmann, R.

We first discuss the progress in linear optics, in particular, the formulation and application of geometrical-optics approximation and its generalization. We then discuss the progress in non-linear optics, in particular, the enhancement of a first-order Freedericksz transition and intrinsic optical bistability in homeotropic and parallel oriented nematic liquid crystal cells. Finally, we discuss the liquid crystal alignment and surface effects on field-induced Freedericksz transition.

Action recognition using mined hierarchical compound features.

PubMed

Gilbert, Andrew; Illingworth, John; Bowden, Richard

2011-05-01

The field of Action Recognition has seen a large increase in activity in recent years. Much of the progress has been through incorporating ideas from single-frame object recognition and adapting them for temporal-based action recognition. Inspired by the success of interest points in the 2D spatial domain, their 3D (space-time) counterparts typically form the basic components used to describe actions, and in action recognition the features used are often engineered to fire sparsely. This is to ensure that the problem is tractable; however, this can sacrifice recognition accuracy as it cannot be assumed that the optimum features in terms of class discrimination are obtained from this approach. In contrast, we propose to initially use an overcomplete set of simple 2D corners in both space and time. These are grouped spatially and temporally using a hierarchical process, with an increasing search area. At each stage of the hierarchy, the most distinctive and descriptive features are learned efficiently through data mining. This allows large amounts of data to be searched for frequently reoccurring patterns of features. At each level of the hierarchy, the mined compound features become more complex, discriminative, and sparse. This results in fast, accurate recognition with real-time performance on high-resolution video. As the compound features are constructed and selected based upon their ability to discriminate, their speed and accuracy increase at each level of the hierarchy. The approach is tested on four state-of-the-art data sets, the popular KTH data set to provide a comparison with other state-of-the-art approaches, the Multi-KTH data set to illustrate performance at simultaneous multiaction classification, despite no explicit localization information provided during training. Finally, the recent Hollywood and Hollywood2 data sets provide challenging complex actions taken from commercial movie sequences. For all four data sets, the proposed hierarchical approach outperforms all other methods reported thus far in the literature and can achieve real-time operation.

Progressive Fracture of Fiber Composite Build-Up Structures

NASA Technical Reports Server (NTRS)

Gotsis, Pascal K.; Chamis, C. C.; Minnetyan, Levon

1997-01-01

Damage progression and fracture of built-up composite structures is evaluated by using computational simulation. The objective is to examine the behavior and response of a stiffened composite (0/ +/- 45/90)(sub s6) laminate panel by simulating the damage initiation, growth, accumulation, progression and propagation to structural collapse. An integrated computer code, CODSTRAN, was augmented for the simulation of the progressive damage and fracture of built-up composite structures under mechanical loading. Results show that damage initiation and progression have significant effect on the structural response. Influence of the type of loading is investigated on the damage initiation, propagation and final fracture of the build-up composite panel.

Progressive Fracture of Fiber Composite Build-Up Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon; Gotsis, Pascal K.; Chamis, C. C.

1997-01-01

Damage progression and fracture of built-up composite structures is evaluated by using computational simulation. The objective is to examine the behavior and response of a stiffened composite (0 +/-45/90)(sub s6) laminate panel by simulating the damage initiation, growth, accumulation, progression and propagation to structural collapse. An integrated computer code CODSTRAN was augmented for the simulation of the progressive damage and fracture of built-up composite structures under mechanical loading. Results show that damage initiation and progression to have significant effect on the structural response. Influence of the type of loading is investigated on the damage initiation, propagation and final fracture of the build-up composite panel.

Monitoring corrosion in reinforced concrete structures

NASA Astrophysics Data System (ADS)

Kung, Peter; Comanici, Maria I.

2014-06-01

Many defects can cause deterioration and cracks in concrete; these are results of poor concrete mix, poor workmanship, inadequate design, shrinkage, chemical and environmental attack, physical or mechanical damage, and corrosion of reinforcing steel (RS). We want to develop a suite of sensors and systems that can detect that corrosion is taking place in RS and inform owners how serious the problem is. By understanding the stages of the corrosion process, we can develop special a sensor that detects each transition. First, moisture ingress can be monitored by a fiber optics humidity sensor, then ingress of Chloride, which acts as a catalyst and accelerates the corrosion process by converting iron into ferrous compounds. We need a fiber optics sensor which can quantify Chloride ingress over time. Converting ferric to ferrous causes large volume expansion and cracks. Such pressure build-up can be detected by a fiber optic pressure sensor. Finally, cracks emit acoustic waves, which can be detected by a high frequency sensor made with phase-shifted gratings. This paper will discuss the progress in our development of these special sensors and also our plan for a field test by the end of 2014. We recommend that we deploy these sensors by visually inspecting the affected area and by identifying locations of corrosion; then, work with the designers to identify spots that would compromise the integrity of the structure; finally, drill a small hole in the concrete and insert these sensors. Interrogation can be done at fixed intervals with a portable unit.

Procedures for Handling Retaliation Complaints Under Section 31307 of the Moving Ahead for Progress in the 21st Century Act (MAP-21). Final rule.

PubMed

2016-12-14

On March 16, 2016, the Occupational Safety and Health Administration (OSHA) of the U.S. Department of Labor (Department) issued an interim final rule (IFR) that provided procedures for the Department's processing of complaints under the employee protection (retaliation or whistleblower) provisions of Section 31307 of the Moving Ahead for Progress in the 21st Century Act (MAP-21). The IFR established procedures and time frames for the handling of retaliation complaints under MAP-21, including procedures and time frames for employee complaints to OSHA, investigations by OSHA, appeals of OSHA determinations to an administrative law judge (ALJ) for a hearing de novo, hearings by ALJs, review of ALJ decisions by the Administrative Review Board (ARB) (acting on behalf of the Secretary of Labor) and judicial review of the Secretary's final decision. It also set forth the Department's interpretations of the MAP-21 whistleblower provisions on certain matters. This final rule adopts, without change, the IFR.

Processing and thermodynamics research, Volume II. Monthly progress report, November 1984

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

Not Available

Data assembly is in progress on the Venezuelan Cerro Negro, California, Wilmington and Mexican Mayan crudes. A draft of a proposal is in preparation that might join this correlational work with complementary correlational work at the University of Oklahoma (Project BPT1). Cerro Negro 200 to 425/sup 0/C and 425 to 550/sup 0/C saturate fractions were analyzed with the CEC 21-103 mass spectrometer using ASTM method D2786, and experiments were devised to establish reproducibility of analyses with the KRATOS MS-50 (Project BPT2). Thermodynamic property measurements on organic nitrogen compounds included a liquid phase heat capacity study of 2,5-dimethylpyridine, and the oxygenmore » sensitivity of phenanthridine was checked prior to bomb calorimetry (Project BPT3A). Heat capacity measurements on chroman are progressing well, and vapor pressure measurements of tetrahydrophenanthrene are in progress (Project BPT3B). Work was begun on the design and procurement of equipment necessary for construction of a bench scale catalytic cracking unit. The supercritical extraction unit is being assembled (Project OPT1). Thiopene separations were begun on Cerro Negro 425 to 550/sup 0/C neutrals, and separation of sulfides from Cerro Negro 550 to 700/sup 0/C and 700+/sup 0/C neutrals was completed (Project OPT2). Preparations for PVT studies of methanol are nearing completion, and a list of critically needed PVT measurements was reviewed to help select the next compound for study. A possible candidate is hydrogen sulfide. (Project OPT3). Good progress continues in the treatment of the RP feed (Project OPT4) to recover Milspec F-76. It is anticipated that 85% recovery is possible by the chemical treatment/distillation process.« less

Region 4: South Carolina Adequate Letter and Response to Comments (6/21/2012)

EPA Pesticide Factsheets

This May 25, 2012 letter from EPA approves South Carolina's reasonable further progress (RFP) plan including the motor vehicle emission budget (MVEB) for volatile organic compounds (VOC) and EPA's response to comments received on the adequacy notification

Evaluating novel synthetic compounds active against Bacillus subtilis and Bacillus cereus spores using Live imaging with SporeTrackerX.

PubMed

Omardien, Soraya; Ter Beek, Alexander; Vischer, Norbert; Montijn, Roy; Schuren, Frank; Brul, Stanley

2018-06-14

An empirical approach was taken to screen a novel synthetic compound library designed to be active against Gram-positive bacteria. We obtained five compounds that were active against spores from the model organism Bacillus subtilis and the food-borne pathogen Bacillus cereus during our population based experiments. Using single cell live imaging we were able to observe effects of the compounds on spore germination and outgrowth. Difference in sensitivity to the compounds could be observed between B. subtilis and B. cereus using live imaging, with minor difference in the minimal inhibitory and bactericidal concentrations of the compounds against the spores. The compounds all delayed the bursting time of germinated spores and affected the generation time of vegetative cells at sub-inhibitory concentrations. At inhibitory concentrations spore outgrowth was prevented. One compound showed an unexpected potential for preventing spore germination at inhibitory concentrations, which merits further investigation. Our study shows the valuable role single cell live imaging can play in the final selection process of antimicrobial compounds.

Preparation of SRN1-type coupling adducts from aliphatic gem-dinitro compounds in ionic liquids.

PubMed

Kamimura, Akio; Toyoshima, Seiichi

2012-04-25

S(RN)1-type coupling adducts are readily prepared by the reaction between a-sulfonylesters or a-cyanosulfones and gem-dinitro compounds in ionic liquids. The reactions progress smoothly and recovered ionic liquids can be used for several iterations, as long as they are washed with water to remove alkali metallic salts. The reaction rate is slower than the corresponding S(RN)1 reaction in DMSO, but no acceleration on irradiation or no inhibition in the presence of m-DNB are observed.

Beyond alkyl transfer: Synthesis of main group metal (Mg, Ca, Zn) silyl and tris(oxazolinyl)borato complexes and their stoichiometric and catalytic reactions with borane Lewis acids and carbonyls

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

Lampland, Nicole Lynn

2015-05-09

Recently, the fundamental knowledge of main group metal chemistry has grown. This progress is crucial for the further development of main group metal compounds in silicon chemistry and catalysis and for advancing their applications as green alternatives to many rare earth and transition metal compounds. This thesis focuses on reactivity beyond the welldocumented alkyl-transfer applications for main group metals, and it highlights examples of reactions with Lewis acids and the reduction of carbonyls.

46. (Credit LSU) High service pumping room, c1904. The # ...

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

46. (Credit LSU) High service pumping room, c1904. The # 1 Worthington horizontal, triple expansion, high service engine is in the background. The pump whose steam end is in the foreground is a Blake compound, duplex horizontal engine, installed c1904. The engine in the center of the illustration is one of the original 1887 Blake high service engines (compound, duplex). It was shortly after removed. (From: Shreveport Progressive League, Shreveport of To-Day, September 1904, p. 47) - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

[Progresses in screening active compounds from herbal medicine by affinity chromatography].

PubMed

Feng, Ying-shu; Tong, Shan-shan; Xu, Xi-ming; Yu, Jiang-nan

2015-03-01

Affinity chromatography is a chromatographic method for separating molecules using the binding characteristics of the stationary phase with potential drug molecules. This method can be performed as a high throughput screening method and a chromatographic separation method to screen a variety of active drugs. This paper summarizes the history of affinity chromatography, screening technology of affinity chromatography, and application of affinity chromatography in screening bio-active compounds in herbal medicines, and then discusses its application prospects, in order to broaden applications of the affinity chromatography in drug screening.

Public health assessment for Pasley Solvents and Chemicals Inc. , Garden City, Nassau County, New York, Region 2. Cerclis No. NYD991292004. Final report

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

Not Available

1994-08-22

The Pasley Solvents and Chemicals site, which is on the National Priorities List, is situated between the borders of the Village of Garden City and Uniondale in the Town of Hempstead, Nassau County, New York. Soils at the site are contaminated with volatile organic compounds (VOCs), primarily solvent constituents and petroleum hydrocarbons compounds; semi-volatile compounds (primarily polycyclic aromatic hydrocarbon compounds); and several metals. Groundwater in the shallow and deep aquifers under the site is contaminated with VOCs, primarily solvent constituents and petroleum hydrocarbons compounds, and two semi-volatile compounds at the concentrations exceeding public health assessment comparison values. Limited information ismore » available on soil gas intrusion and indoor air contamination, and this pathway is of concern since occupied buildings are nearby and above contaminated groundwater plumes.« less

Antimicrobial activity-guided identification of compounds from the deciduous leaves of Malus doumeri by HPLC-ESI-QTOF-MS/MS.

PubMed

Shen, Bingbing; Zhou, Rongrong; Yang, Yupei; Li, Jiayu; Liang, Xuejuan; Chen, Lin; Huang, Luqi; Zhang, Shuihan

2018-04-03

This paper intends to identify the antimicrobial activity compounds from the deciduous leaves of Malus doumeri (Dong Li Tea) by HPLC-ESI-QTOF-MS/MS. The ethanol extracts of Malus doumeri were partitioned into petroleum ether, dichloromethane, ethyl acetate, n-butanol and water fraction, respectively. The antimicrobial screening experiments showed that ethyl acetate fraction has a certain antibacterial activity by inhibition zone method in vitro. And then we used the HPLC-ESI-QTOF-MS/MS method to verify the identities of bioactive compounds. Finally, 41 compounds were determined and 11 of which were firstly reported in this plant. Notably, compounds (32, 34, 38) are new dihydrochalcones, and three chlorogenic acid analogues (10, 13, 17) may be potential antimicrobial active ingredient. Which is of great significance to the isolation of novel compounds and the discovery of new natural preservative candidates from the deciduous leaves of Malus doumeri.

Functional annotation of chemical libraries across diverse biological processes.

PubMed

Piotrowski, Jeff S; Li, Sheena C; Deshpande, Raamesh; Simpkins, Scott W; Nelson, Justin; Yashiroda, Yoko; Barber, Jacqueline M; Safizadeh, Hamid; Wilson, Erin; Okada, Hiroki; Gebre, Abraham A; Kubo, Karen; Torres, Nikko P; LeBlanc, Marissa A; Andrusiak, Kerry; Okamoto, Reika; Yoshimura, Mami; DeRango-Adem, Eva; van Leeuwen, Jolanda; Shirahige, Katsuhiko; Baryshnikova, Anastasia; Brown, Grant W; Hirano, Hiroyuki; Costanzo, Michael; Andrews, Brenda; Ohya, Yoshikazu; Osada, Hiroyuki; Yoshida, Minoru; Myers, Chad L; Boone, Charles

2017-09-01

Chemical-genetic approaches offer the potential for unbiased functional annotation of chemical libraries. Mutations can alter the response of cells in the presence of a compound, revealing chemical-genetic interactions that can elucidate a compound's mode of action. We developed a highly parallel, unbiased yeast chemical-genetic screening system involving three key components. First, in a drug-sensitive genetic background, we constructed an optimized diagnostic mutant collection that is predictive for all major yeast biological processes. Second, we implemented a multiplexed (768-plex) barcode-sequencing protocol, enabling the assembly of thousands of chemical-genetic profiles. Finally, based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality. Applying this high-throughput approach, we screened seven different compound libraries and annotated their functional diversity. We further validated biological process predictions, prioritized a diverse set of compounds, and identified compounds that appear to have dual modes of action.

A trisubstituted pyrazole derivative reduces DMBA-induced mammary tumor growth in rats by inhibiting estrogen receptor-α expression.

PubMed

Ananda, Hanumappa; Sharath Kumar, Kothanahally S; Sudhanva, Muddenahalli S; Rangappa, Shobith; Rangappa, Kanchugarakoppal S

2018-05-18

Aberrant expression of estrogen receptor alpha (ER-α) is observed in many pathological complications like breast cancer, endometrial cancer, and in osteoporosis. ER-α plays a vital role in the initiation and progression of breast cancer and confers chemo and radioresistance to the cancer cells by upregulating expression of anti-apoptotic proteins. The synthetic pyrazole derivative 3-(1-(4-bromophenyl)-5-phenyl-1H-pyrazol-3-yl)pyridine (compound 5d) displays significant cytotoxicity against mammary carcinoma cells. Molecular docking studies revealed that compound 5d binds to ligand binding domain of (ER-α). In vivo studies were carried out to investigate ER-α expression by immunohistochemistry and quantitative RT-PCR, which revealed reduction of ER-α in tumor cells upon treatment with compound 5d indicating its ER-α antagonistic effect. Our study ascertains compound 5d as a potent inhibitor of mammary carcinoma cells.

Bead-based screening in chemical biology and drug discovery.

PubMed

Komnatnyy, Vitaly V; Nielsen, Thomas E; Qvortrup, Katrine

2018-06-11

High-throughput screening is an important component of the drug discovery process. The screening of libraries containing hundreds of thousands of compounds requires assays amenable to miniaturisation and automization. Combinatorial chemistry holds a unique promise to deliver structurally diverse libraries for early drug discovery. Among the various library forms, the one-bead-one-compound (OBOC) library, where each bead carries many copies of a single compound, holds the greatest potential for the rapid identification of novel hits against emerging drug targets. However, this potential has not yet been fully realized due to a number of technical obstacles. In this feature article, we review the progress that has been made in bead-based library screening and its application to the discovery of bioactive compounds. We identify the key challenges of this approach and highlight key steps needed for making a greater impact in the field.

Expanding frontiers in materials chemistry and physics with multiple anions.

PubMed

Kageyama, Hiroshi; Hayashi, Katsuro; Maeda, Kazuhiko; Attfield, J Paul; Hiroi, Zenji; Rondinelli, James M; Poeppelmeier, Kenneth R

2018-02-22

During the last century, inorganic oxide compounds laid foundations for materials synthesis, characterization, and technology translation by adding new functions into devices previously dominated by main-group element semiconductor compounds. Today, compounds with multiple anions beyond the single-oxide ion, such as oxyhalides and oxyhydrides, offer a new materials platform from which superior functionality may arise. Here we review the recent progress, status, and future prospects and challenges facing the development and deployment of mixed-anion compounds, focusing mainly on oxide-derived materials. We devote attention to the crucial roles that multiple anions play during synthesis, characterization, and in the physical properties of these materials. We discuss the opportunities enabled by recent advances in synthetic approaches for design of both local and overall structure, state-of-the-art characterization techniques to distinguish unique structural and chemical states, and chemical/physical properties emerging from the synergy of multiple anions for catalysis, energy conversion, and electronic materials.

DEGAS: sharing and tracking target compound ideas with external collaborators.

PubMed

Lee, Man-Ling; Aliagas, Ignacio; Dotson, Jennafer; Feng, Jianwen A; Gobbi, Alberto; Heffron, Timothy

2012-02-27

To minimize the risk of failure in clinical trials, drug discovery teams must propose active and selective clinical candidates with good physicochemical properties. An additional challenge is that today drug discovery is often conducted by teams at different geographical locations. To improve the collaborative decision making on which compounds to synthesize, we have implemented DEGAS, an application which enables scientists from Genentech and from collaborating external partners to instantly access the same data. DEGAS was implemented to ensure that only the best target compounds are made and that they are made without duplicate effort. Physicochemical properties and DMPK model predictions are computed for each compound to allow the team to make informed decisions when prioritizing. The synthesis progress can be easily tracked. While developing DEGAS, ease of use was a particular goal in order to minimize the difficulty of training and supporting remote users.

Bioactive Compounds Found in Brazilian Cerrado Fruits

PubMed Central

Bailão, Elisa Flávia Luiz Cardoso; Devilla, Ivano Alessandro; da Conceição, Edemilson Cardoso; Borges, Leonardo Luiz

2015-01-01

Functional foods include any natural product that presents health-promoting effects, thereby reducing the risk of chronic diseases. Cerrado fruits are considered a source of bioactive substances, mainly phenolic compounds, making them important functional foods. Despite this, the losses of natural vegetation in the Cerrado are progressive. Hence, the knowledge propagation about the importance of the species found in Cerrado could contribute to the preservation of this biome. This review provides information about Cerrado fruits and highlights the structures and pharmacologic potential of functional compounds found in these fruits. Compounds detected in Caryocar brasiliense Camb. (pequi), Dipteryx alata Vog. (baru), Eugenia dysenterica DC. (cagaita), Eugenia uniflora L. (pitanga), Genipa americana L. (jenipapo), Hancornia speciosa Gomes (mangaba), Mauritia flexuosa L.f. (buriti), Myrciaria cauliflora (DC) Berg (jabuticaba), Psidium guajava L. (goiaba), Psidium spp. (araçá), Solanum lycocarpum St. Hill (lobeira), Spondias mombin L. (cajá), Annona crassiflora Mart. (araticum), among others are reported here. PMID:26473827

Nature as a source of metabolites with cholinesterase-inhibitory activity: an approach to Alzheimer's disease treatment.

PubMed

Pinho, Brígida R; Ferreres, Federico; Valentão, Patrícia; Andrade, Paula B

2013-12-01

Alzheimer's disease (AD) is the most common cause of dementia, being responsible for high healthcare costs and familial hardships. Despite the efforts of researchers, no treatment able to delay or stop AD progress exists. Currently, the available treatments are only symptomatic, cholinesterase inhibitors being the most widely used drugs. Here we describe several natural compounds with anticholinesterase (acetylcholinesterase and butyrylcholinesterase) activity and also some synthetic compounds whose structures are based on those of natural compounds. Galantamine and rivastigmine are two cholinesterase inhibitors used in therapeutics: galantamine is a natural alkaloid that was extracted for the first time from Galanthus nivalis L., while rivastigmine is a synthetic alkaloid, the structure of which is modelled on that of natural physostigmine. Alkaloids include a high number of compounds with anticholinesterases activity at the submicromolar range. Quinones and stilbenes are less well studied regarding cholinesterase inhibition, although some of them, such as sargaquinoic acid or (+)-α-viniferin, show promising activity. Among flavonoids, flavones and isoflavones are the most potent compounds. Xanthones and monoterpenes are generally weak cholinesterase inhibitors. Nature is an almost endless source of bioactive compounds. Several natural compounds have anticholinesterase activity and others can be used as leader compounds for the synthesis of new drugs. © 2013 Royal Pharmaceutical Society.

Axonal Transport and Neurodegeneration: How Marine Drugs Can Be Used for the Development of Therapeutics

PubMed Central

White, Joseph A.; Banerjee, Rupkatha; Gunawardena, Shermali

2016-01-01

Unlike virtually any other cells in the human body, neurons are tasked with the unique problem of transporting important factors from sites of synthesis at the cell bodies, across enormous distances, along narrow-caliber projections, to distally located nerve terminals in order to maintain cell viability. As a result, axonal transport is a highly regulated process whereby necessary cargoes of all types are packaged and shipped from one end of the neuron to the other. Interruptions in this finely tuned transport have been linked to many neurodegenerative disorders including Alzheimer’s (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) suggesting that this pathway is likely perturbed early in disease progression. Therefore, developing therapeutics targeted at modifying transport defects could potentially avert disease progression. In this review, we examine a variety of potential compounds identified from marine aquatic species that affect the axonal transport pathway. These compounds have been shown to function in microtubule (MT) assembly and maintenance, motor protein control, and in the regulation of protein degradation pathways, such as the autophagy-lysosome processes, which are defective in many degenerative diseases. Therefore, marine compounds have great potential in developing effective treatment strategies aimed at early defects which, over time, will restore transport and prevent cell death. PMID:27213408

Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action

PubMed Central

Aung, Thazin Nwe; Qu, Zhipeng; Kortschak, R. Daniel; Adelson, David L.

2017-01-01

Many approaches to cancer management are often ineffective due to adverse reactions, drug resistance, or inadequate target specificity of single anti-cancer agents. In contrast, a combinatorial approach with the application of two or more anti-cancer agents at their respective effective dosages can achieve a synergistic effect that boosts cytotoxicity to cancer cells. In cancer, aberrant apoptotic pathways allow cells that should be killed to survive with genetic abnormalities, leading to cancer progression. Mutations in apoptotic mechanism arising during the treatment of cancer through cancer progression can consequently lead to chemoresistance. Natural compound mixtures that are believed to have multiple specific targets with minimal acceptable side-effects are now of interest to many researchers due to their cytotoxic and chemosensitizing activities. Synergistic interactions within a drug mixture enhance the search for potential molecular targets in cancer cells. Nonetheless, biased/flawed scientific evidence from natural products can suggest false positive therapeutic benefits during drug screening. In this review, we have taken these factors into consideration when discussing the evidence for these compounds and their synergistic therapeutic benefits in cancer. While there is limited evidence for clinical efficacy for these mixtures, in vitro data suggest that these preparations merit further investigation, both in vitro and in vivo. PMID:28304343

Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action.

PubMed

Aung, Thazin Nwe; Qu, Zhipeng; Kortschak, R Daniel; Adelson, David L

2017-03-17

Many approaches to cancer management are often ineffective due to adverse reactions, drug resistance, or inadequate target specificity of single anti-cancer agents. In contrast, a combinatorial approach with the application of two or more anti-cancer agents at their respective effective dosages can achieve a synergistic effect that boosts cytotoxicity to cancer cells. In cancer, aberrant apoptotic pathways allow cells that should be killed to survive with genetic abnormalities, leading to cancer progression. Mutations in apoptotic mechanism arising during the treatment of cancer through cancer progression can consequently lead to chemoresistance. Natural compound mixtures that are believed to have multiple specific targets with minimal acceptable side-effects are now of interest to many researchers due to their cytotoxic and chemosensitizing activities. Synergistic interactions within a drug mixture enhance the search for potential molecular targets in cancer cells. Nonetheless, biased/flawed scientific evidence from natural products can suggest false positive therapeutic benefits during drug screening. In this review, we have taken these factors into consideration when discussing the evidence for these compounds and their synergistic therapeutic benefits in cancer. While there is limited evidence for clinical efficacy for these mixtures, in vitro data suggest that these preparations merit further investigation, both in vitro and in vivo.

Targeting androgen receptor and JunD interaction for prevention of prostate cancer progression.

PubMed

Mehraein-Ghomi, Farideh; Kegel, Stacy J; Church, Dawn R; Schmidt, Joseph S; Reuter, Quentin R; Saphner, Elizabeth L; Basu, Hirak S; Wilding, George

2014-05-01

Multiple studies show that reactive oxygen species (ROS) play a major role in prostate cancer (PCa) development and progression. Previously, we reported an induction of Spermidine/Spermine N(1) -Acetyl Transferase (SSAT) by androgen-activated androgen receptor (AR)-JunD protein complex that leads to over-production of ROS in PCa cells. In our current research, we identify small molecules that specifically block AR-JunD in this ROS-generating metabolic pathway. A high throughput assay based on Gaussia Luciferase reconstitution was used to identify inhibitors of the AR-JunD interaction. Selected hits were further screened using a fluorescence polarization competitor assay to eliminate those that bind to the AR Ligand Binding Domain (LBD), in order to identify molecules that specifically target events downstream to androgen activation of AR. Eleven molecules were selected for studies on their efficacy against ROS generation and growth of cultured human PCa cells by DCFH dye-oxidation assay and DNA fluorescence assay, respectively. In situ Proximity Ligation Assay (PLA), SSAT promoter-luciferase reporter assay, and western blotting of apoptosis and cell cycle markers were used to study mechanism of action of the lead compound. Selected lead compound GWARJD10 with EC(50) 10 μM against ROS production was shown to block AR-JunD interaction in situ as well as block androgen-induced SSAT gene expression at IC(50) 5 μM. This compound had no effect on apoptosis markers, but reduced cyclin D1 protein level. Inhibitor of AR-JunD interaction, GWARJD10 shows promise for prevention of progression of PCa at an early stage of the disease by blocking growth and ROS production. © 2014 Wiley Periodicals, Inc.

AN INVENTORY OF SOURCES AND ENVIRONMENTAL RELEASES OF DIOXIN-LIKE COMPOUNDS IN THE U.S. FOR THE YEARS 1987, 1995, AND 2000 (Final, Nov 2006)

EPA Science Inventory

An Inventory of Sources and Environmental Releases of Dioxin-Like Compounds in the United States for the Years 1987, 1995, and 2000 (EPA/600/P-03/002F, November 2006), is a peer reviewed report representing EPA’s assessment of dioxin sources and their emissions to the environment...

Support services relating to geothermal programs. Final report

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

Not Available

1981-08-01

Activities designed to assist in the assessment of processes through which geopressured methane production and geopressure-geothermal power can be increased are discussed. Progress is reported on the following: general support, hot-dry-rock review, R and D plan, and the Edna Delcambre final report. (MHR)

Uncertainty and Variability in Physiologically-Based Pharmacokinetic (PBPK) Models: Key Issues and Case Studies (Final Report)

EPA Science Inventory

EPA announced the availability of the final report, Uncertainty and Variability in Physiologically-Based Pharmacokinetic (PBPK) Models: Key Issues and Case Studies. This report summarizes some of the recent progress in characterizing uncertainty and variability in physi...

Renal studies in safety pharmacology and toxicology: A survey conducted in the top 15 pharmaceutical companies.

PubMed

Benjamin, Amanda; Gallacher, David J; Greiter-Wilke, Andrea; Guillon, Jean-Michel; Kasai, Cheiko; Ledieu, David; Levesque, Paul; Prelle, Katja; Ratcliffe, Sian; Sannajust, Frederick; Valentin, Jean-Pierre

2015-01-01

With the recent development of more sensitive biomarkers to assess kidney injury preclinically, a survey was designed i) to investigate what strategies are used to investigate renal toxicity in both ICH S7A compliant Safety Pharmacology (SP) studies after a single dose of a compound and within repeat-dose toxicity studies by large pharmaceutical companies today; ii) to understand whether renal SP studies have impact or utility in drug development and/or if it may be more appropriate to assess renal effects after multiple doses of compounds; iii) to ascertain how much mechanistic work is performed by the top 15 largest pharmaceutical companies (as determined by R&D revenue size); iv) to gain an insight into the impact of the validation of DIKI biomarkers and their introduction in the safety evaluation paradigm; and v) to understand the impact of renal/urinary safety study data on progression of projects. Two short anonymous surveys were submitted to SP leaders of the top 15 pharmaceutical companies, as defined by 2012 R&D portfolio size. Fourteen multiple choice questions were designed to explore the strategies used to investigate renal effects in both ICH S7A compliant SP studies and within toxicology studies. A 67% and 60% response rate was obtained in the first and second surveys, respectively. Nine out of ten respondent companies conduct renal excretory measurements (eg. urine analysis) in toxicology studies whereas only five out of ten conduct specific renal SP studies; and all of those 5 also conduct the renal excretory measurements in toxicology studies. These companies measure and/or calculate a variety of parameters as part of these studies, and also on a case by case basis include regulatory qualified and non-qualified DIKI biomarkers. Finally, only one company has used renal/urinary functional data alone to stop a project, whereas the majority of respondents combine renal data with other target organ assessments to form an integrated decision-making set. These short surveys highlighted areas of similarity: a) urinary measurements are most commonly taken on repeat-dose toxicity studies, and b) renal SP studies are less often utilised. The two major differences are a) lack of consistent use of DIKI biomarkers in urinary safety studies and b) the way large pharmaceutical companies assess renal function. Finally, suggestions were made to improve the safety assessment methods for determining the safety of compounds with potential renal liability. Copyright © 2015 Elsevier Inc. All rights reserved.

Experimental and Theoretical Progress on the GEM Theory

NASA Astrophysics Data System (ADS)

Brandenburg, J. E.

This paper reports experimental and theoretical progress on the GEM unification theory. In theoretical progress, the derivation of the GEM theory using it in a fully covariant form is achieved based on the principle of self-cancellation of the ZPF EM stress-momentum tensor. This derivation reveals that the final Gravity-EM system obeys a Helmholtz-like equation resembling that governing sound propagation. Finally an improved derivation of the formula for the Newton Gravitation constant is shown, qresulting in the formula G = e2/(4πɛ0 me mp) α exp (-2 (α-.86/σ2…) = 6.673443 x10-11 N-m2 kg-2 that agrees with experimental values to 3 parts per 100,000. Experiments have found parity violating weight reductions in gyroscopes driven by rotating EM fields. These experiments appear to confirm gravity modification using electromagnetism predicted by the GEM theory through the Vacuum Bernoulli Equation.

Friedrich Nietzsche's mental illness--general paralysis of the insane vs. frontotemporal dementia.

PubMed

Orth, M; Trimble, M R

2006-12-01

For a long time it was thought that Nietzsche suffered from general paralysis of the insane (GPI). However, this diagnosis has been questioned recently, and alternative diagnoses have been proposed. We have charted Friedrich Nietzsche's final fatal illness, and viewed the differential diagnosis in the light of recent neurological understandings of dementia syndromes. It is unclear that Nietzsche ever had syphilis. He lacked progressive motor and other neurological features of a progressive syphilitic central nervous system (CNS) infection and lived at least 12 years following the onset of his CNS signs, which would be extremely rare for patients with untreated GPI. Finally, his flourish of productivity in 1888 would be quite uncharacteristic of GPI, but in keeping with reports of burgeoning creativity at some point in the progression of frontotemporal dementia (FTD). We suggest that Nietzsche did not have GPI, but died from a chronic dementia, namely FTD.

Perspectives on Progress: The School-to-Work National Customer Dialogues. Final Report.

ERIC Educational Resources Information Center

Public Forum Inst., Washington, DC.

"Perspectives on Progress: The School-to-Work (STW) National Customer Dialogues" was a series of six regional and two national discussions that were held between December 1999 and July 2000 to gather the views of more than 700 employers, educators, labor union representatives, students, parents, community-based organizations, and state…

Stage Theory and Research on Tobacco, Alcohol, and Other Drug Use.

ERIC Educational Resources Information Center

Werch, Chudley E.; Anzalone, Debra

1995-01-01

Examines the conceptual and empirical foundations of individual drug use stage development and progression related to tobacco, alcohol, and other drugs. Research examining interdrug use progression among youths supports the idea of a generally invariant sequence, involving nonuse to legal drug use, marijuana, and finally other illegal drug use.…

Development of Career Progression Systems for Employees in the Foodservice Industry. Final Report.

ERIC Educational Resources Information Center

National Restaurant Association, Chicago, IL.

Firms representing four segments of the foodservice industry (institutional foodservice (9 jobs), commercial restaurants (19 jobs), hotel foodservice (100 jobs), and airline foodservice (10 jobs), participated in a career and training study to test the feasibility of designing and implementing career progression (c.p.) systems within these…

Progress Report: Access and Persistence of Minority Students in the Arizona Universities.

ERIC Educational Resources Information Center

Cotera, Augustus S.; And Others

One of the working papers in the final report of the Arizona Board of Regents' Task Force on Excellence, Efficiency and Competitiveness, this report presents statistical information on the progress of minority student access and persistence in the three Arizona Universities, Arizona's community colleges, and the Arizona Department of Education.…

THE U.S. ENVIRONMENTAL PROTECTION AGENCY PARTICULATE MATTER HEALTH EFFECTS RESEARCH CENTERS PROGRAM: A MIDCOURSE REPORT OF STATUS, PROGRESS, AND PLANS. (R827351)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Data on volatile compounds in fermented materials used for salmon fish sauce production.

PubMed

Nakano, Mitsutoshi; Sagane, Yoshimasa; Koizumi, Ryosuke; Nakazawa, Yozo; Yamazaki, Masao; Watanabe, Toshihiro; Takano, Katsumi; Sato, Hiroaki

2018-02-01

This article describes the analysis of volatile compounds in fermented materials used for salmon fish sauce production via gas chromatography/mass spectrometry (GC/MS). Ten types of fish sauces were produced from raw salmon materials, including various proportions of flesh, viscera, inedible portion (heads, fins, and backbones), and soft roe, by mixing them with salt and allowing them to ferment for up to three months. The volatile compounds were captured by a solid-phase microextraction method and then applied to GC/MS for separation and identification of the compounds in the fish sauce products. The number of volatile compounds identified in the starting materials varied from 15 to 29 depending on the ingredients. The number of compounds in the final fish sauce products was reduced by 3.4-94.7% of that in the original material. The retention times and names of the identified compounds, as well as their relative peak areas, are provided in a Microsoft Excel Worksheet.

Clinical features of Friedreich's ataxia: classical and atypical phenotypes.

PubMed

Parkinson, Michael H; Boesch, Sylvia; Nachbauer, Wolfgang; Mariotti, Caterina; Giunti, Paola

2013-08-01

One hundred and fifty years since Nikolaus Friedreich's first description of the degenerative ataxic syndrome which bears his name, his description remains at the core of the classical clinical phenotype of gait and limb ataxia, poor balance and coordination, leg weakness, sensory loss, areflexia, impaired walking, dysarthria, dysphagia, eye movement abnormalities, scoliosis, foot deformities, cardiomyopathy and diabetes. Onset is typically around puberty with slow progression and shortened life-span often related to cardiac complications. Inheritance is autosomal recessive with the vast majority of cases showing an unstable intronic GAA expansion in both alleles of the frataxin gene on chromosome 9q13. A small number of cases are caused by a compound heterozygous expansion with a point mutation or deletion. Understanding of the underlying molecular biology has enabled identification of atypical phenotypes with late onset, or atypical features such as retained reflexes. Late-onset cases tend to have slower progression and are associated with smaller GAA expansions. Early-onset cases tend to have more rapid progression and a higher frequency of non-neurological features such as diabetes, cardiomyopathy, scoliosis and pes cavus. Compound heterozygotes, including those with large deletions, often have atypical features. In this paper, we review the classical and atypical clinical phenotypes of Friedreich's ataxia. © 2013 International Society for Neurochemistry.

Progress in the synthesis of 1-O-methylchlorogenic acid

USDA-ARS?s Scientific Manuscript database

Antioxidant properties of phenolic compounds have been implicated in the slowing or prevention of a variety of human diseases such as hypertention, inflammation, and cancer. Investigation of the antioxidant behavior of plant phenolics remains an important area of investigation in human food and heal...

Targeting Matrix Metalloproteinases in Cancer: Bringing New Life to Old Ideas.

PubMed

Cathcart, Jillian; Pulkoski-Gross, Ashleigh; Cao, Jian

2015-03-01

Since the identification of matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, as being a driving factor for cancer progression and patient prognosis, MMPs have been studied extensively. Although early programs targeting MMPs were largely unsuccessful in clinical trials, they remain a viable and highly desirable therapeutic target based on preclinical studies and their role in disease progression. As information regarding the structure and function of these proteinases is compiled and biotechnology evolves, tools to develop better inhibitors is within our grasp. Improved methods for high throughput screening and in silico drug design programs have identified compounds which are highly potent, have high binding affinities, and exhibit favorable pharmacokinetic profiles. More recently, advances in drug delivery methods or compounds which bind outside the active site have brought new light to the field. In this review, we highlight the role of MMPs in cancer, clinical trials for MMP inhibitors, and novel approaches to targeting MMPs in cancer.

Discovery and Development of ATP-Competitive mTOR Inhibitors Using Computational Approaches.

PubMed

Luo, Yao; Wang, Ling

2017-11-16

The mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism, and angiogenesis. This protein is an attractive target for new anticancer drug development. Significant progress has been made in hit discovery, lead optimization, drug candidate development and determination of the three-dimensional (3D) structure of mTOR. Computational methods have been applied to accelerate the discovery and development of mTOR inhibitors helping to model the structure of mTOR, screen compound databases, uncover structure-activity relationship (SAR) and optimize the hits, mine the privileged fragments and design focused libraries. Besides, computational approaches were also applied to study protein-ligand interactions mechanisms and in natural product-driven drug discovery. Herein, we survey the most recent progress on the application of computational approaches to advance the discovery and development of compounds targeting mTOR. Future directions in the discovery of new mTOR inhibitors using computational methods are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Progress in the Visualization and Mining of Chemical and Target Spaces.

PubMed

Medina-Franco, José L; Aguayo-Ortiz, Rodrigo

2013-12-01

Chemogenomics is a growing field that aims to integrate the chemical and target spaces. As part of a multi-disciplinary effort to achieve this goal, computational methods initially developed to visualize the chemical space of compound collections and mine single-target structure-activity relationships, are being adapted to visualize and mine complex relationships in chemogenomics data sets. Similarly, the growing evidence that clinical effects are many times due to the interaction of single or multiple drugs with multiple targets, is encouraging the development of novel methodologies that are integrated in multi-target drug discovery endeavors. Herein we review advances in the development and application of approaches to generate visual representations of chemical space with particular emphasis on methods that aim to explore and uncover relationships between chemical and target spaces. Also, progress in the data mining of the structure-activity relationships of sets of compounds screened across multiple targets are discussed in light of the concept of activity landscape modeling. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Indoor chemistry: research opportunities and challenges.

PubMed

Nazaroff, W W; Goldstein, A H

2015-08-01

In this editorial, we have highlighted key research opportunities and challenges in four topical themes for indoor chemistry: human occupants as agents influencing indoor chemistry; oxidative chemistry; surface phenomena; and semivolatile organic compounds. In each case, enough prior work has been done to demonstrate the importance of the theme and to create a foundation for future studies. Extensive achievements and ongoing progress in (outdoor) atmospheric chemistry—both in the analytical methods developed and in the scientific knowledge created—also contribute to a strong foundation from which to achieve rapid research progress in this exciting new domain.

Completion of the 1:1,500,000-Scale Geologic Map of Western Libya Montes and Northwestern Tyrrhena Terra

NASA Astrophysics Data System (ADS)

Huff, A. E.; Skinner, J. A.

2018-06-01

Final progress report on the 1:1,500,000-scale mapping of western Libya Montes and northwestern Tyrrhena Terra. The final unit names, labels, and descriptions are reported as well as the methodology for age determinations and brief geologic history.

40 CFR 123.45 - Noncompliance and program reporting by the Director.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) WATER PROGRAMS STATE PROGRAM REQUIREMENTS Transfer of Information and Permit Review § 123.45... schedule report for final compliance or a monitoring report. This applies when the permittee has failed to submit a final compliance schedule progress report, pretreatment report, or a Discharge Monitoring Report...

40 CFR 123.45 - Noncompliance and program reporting by the Director.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) WATER PROGRAMS STATE PROGRAM REQUIREMENTS Transfer of Information and Permit Review § 123.45... schedule report for final compliance or a monitoring report. This applies when the permittee has failed to submit a final compliance schedule progress report, pretreatment report, or a Discharge Monitoring Report...

40 CFR 123.45 - Noncompliance and program reporting by the Director.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) WATER PROGRAMS STATE PROGRAM REQUIREMENTS Transfer of Information and Permit Review § 123.45... schedule report for final compliance or a monitoring report. This applies when the permittee has failed to submit a final compliance schedule progress report, pretreatment report, or a Discharge Monitoring Report...

40 CFR 123.45 - Noncompliance and program reporting by the Director.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) WATER PROGRAMS STATE PROGRAM REQUIREMENTS Transfer of Information and Permit Review § 123.45... schedule report for final compliance or a monitoring report. This applies when the permittee has failed to submit a final compliance schedule progress report, pretreatment report, or a Discharge Monitoring Report...

A Convenient Route to [68Ga]Ga-MAA for Use as a Particulate PET Perfusion Tracer

PubMed Central

Mathias, Carla J.; Green, Mark A.

2008-01-01

A convenient method is described for compounding [68Ga]Ga-MAA (MAA = macroaggregated human serum albumin) with the eluate of a commercially available TiO2-based 68Ge/68Ga generator. The final [68Ga]Ga-MAA product was obtained with an 81.6 ± 5.3% decay-corrected radiochemical yield and a radiochemical purity of 99.8 ± 0.1% (n = 5). Microscopic examination showed the [68Ga]Ga-MAA product to remain within the original particle size range. The entire procedure, from generator elution to delivery of the final [68Ga]Ga-MAA suspension, could be completed in 25 minutes. Only 4.4 ± 0.9% of the total 68Ge breakthrough remaining associated with the final [68Ga]Ga-MAA product. The procedure allows reasonably convenient preparation of [68Ga]Ga-MAA in a fashion that can be readily adapted to sterile product compounding for human use. PMID:18640845

Progressive Fracture of Fiber Composite Builtup Structures

NASA Technical Reports Server (NTRS)

Gotsis, Pascal K.; Chamis, Christos C.; Minnetyan, Levon

1996-01-01

The damage progression and fracture of builtup composite structures was evaluated by using computational simulation to examine the behavior and response of a stiffened composite (0 +/- 45/90)(sub s6) laminate panel subjected to a bending load. The damage initiation, growth, accumulation, progression, and propagation to structural collapse were simulated. An integrated computer code (CODSTRAN) was augmented for the simulation of the progressive damage and fracture of builtup composite structures under mechanical loading. Results showed that damage initiation and progression have a significant effect on the structural response. Also investigated was the influence of different types of bending load on the damage initiation, propagation, and final fracture of the builtup composite panel.

Magnolol Inhibits the Growth of Non-Small Cell Lung Cancer via Inhibiting Microtubule Polymerization.

PubMed

Shen, Jia; Ma, Hailin; Zhang, Tiancheng; Liu, Hui; Yu, Linghua; Li, Guosheng; Li, Huishuang; Hu, Meichun

2017-01-01

The tubulin/microtubule system, which is an integral component of the cytoskeleton, plays an essential role in mitosis. Targeting mitotic progression by disturbing microtubule dynamics is a rational strategy for cancer treatment. Microtubule polymerization assay was performed to examine the effect of Magnolol (a novel natural phenolic compound isolated from Magnolia obovata) on cellular microtubule polymerization in human non-small cell lung cancer (NSCLC) cells. Cell cycle analysis, mitotic index assay, cell proliferation assay, colony formation assay, western blotting analysis of cell cycle regulators, Annexin V-FITC/PI staining, and live/dead viability staining were carried out to investigate the Magnolol's inhibitory effect on proliferation and viability of NSCLS cells in vitro. Xenograft model of human A549 NSCLC tumor was used to determine the Magnolol's efficacy in vivo. Magnolol treatment effectively inhibited cell proliferation and colony formation of NSCLC cells. Further study proved that Magnolol induced the mitotic phase arrest and inhibited G2/M progression in a dose-dependent manner, which were mechanistically associated with expression alteration of a series of cell cycle regulators. Furthermore, Magnolol treatment disrupted the cellular microtubule organization via inhibiting the polymerization of microtubule. We also found treatment with NSCLC cells with Magnolol resulted in apoptosis activation through a p53-independent pathway, and autophgy induction via down-regulation of the Akt/mTOR pathway. Finally, Magnolol treatment significantly suppressed the NSCLC tumor growth in mouse xenograft model in vivo. These findings identify Magnolol as a promising candidate with anti-microtubule polymerization activity for NSCLC treatment. © 2017 The Author(s). Published by S. Karger AG, Basel.

Novel Psychoactive Substances—Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs

PubMed Central

Hassan, Zurina; Bosch, Oliver G.; Singh, Darshan; Narayanan, Suresh; Kasinather, B. Vicknasingam; Seifritz, Erich; Kornhuber, Johannes; Quednow, Boris B.; Müller, Christian P.

2017-01-01

A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug’s properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine (“Kratom”), synthetic cannabinoids (e.g., “Spice”), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications. PMID:28868040

Method of upgrading oils containing hydroxyaromatic hydrocarbon compounds to highly aromatic gasoline

DOEpatents

Baker, Eddie G.; Elliott, Douglas C.

1993-01-01

The present invention is a multi-stepped method of converting an oil which is produced by various biomass and coal conversion processes and contains primarily single and multiple ring hydroxyaromatic hydrocarbon compounds to highly aromatic gasoline. The single and multiple ring hydroxyaromatic hydrocarbon compounds in a raw oil material are first deoxygenated to produce a deoxygenated oil material containing single and multiple ring aromatic compounds. Then, water is removed from the deoxygenated oil material. The next step is distillation to remove the single ring aromatic compouns as gasoline. In the third step, the multiple ring aromatics remaining in the deoxygenated oil material are cracked in the presence of hydrogen to produce a cracked oil material containing single ring aromatic compounds. Finally, the cracked oil material is then distilled to remove the single ring aromatics as gasoline.

IRIS Toxicological Review of Cerium Oxide and Cerium ...

EPA Pesticide Factsheets

On September 29, 2009, the IRIS Summary and Toxicological Review of Cerium Oxide and Cerium Compounds was finalized and loaded onto the IRIS database. The Toxicological Review of Cerium Oxide and Cerium Compounds was reviewed internally by EPA, by other federal agencies and White House Offices, by expert external peer reviewers, and by the public. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency draft of the Cerium Oxide and Cerium Compounds IRIS assessment are posted on this site. The draft Toxicological Review of Cerium Oxide and Cerium Compounds provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to chronic exposure to cerium oxide and cerium compounds.

RAMBAs for Breast Cancer Prevention and Treatment

DTIC Science & Technology

2009-01-01

activated by CYPs only in cancer cells. Finally, the expression of CYPs within tumors has been utilized in the development of bioreductive molecules...enable us to utilize the Catalyst molecular modeling program to create a general phar- macophore model that can differentiate compounds as active or...the discovery and char- acterization of retinoid receptor and the realization of these compounds as nonsteroidal small-molecule hor- mones .1 All-trans

European Science Notes. Volume 39, Number 10.

DTIC Science & Technology

1985-10-01

A.T. Hubbard (Santa Barbara, US), Electro- MODULEF--A MODULAR FINITE ELEMENT PRO- sorption at Well-Defined Surfaces; D.H. GRAM PACKAGE Kolb (Berlin...was described as having one sorption . of the highest theoretical energy densi- Finally, Despi6 described engineer- ties, about 2600 Wh/kg--a value 150...organic compounds , can be varied by compound these transport agents into changing the high temperature treatment organic solutions exhibiting high

Evaluation of Chemically-Sensitive Field-Effect Transistors for Detection of Organophosphorus Compounds

DTIC Science & Technology

1989-12-05

during past decade. In order to understand the basic operation of these sensors, especially of the CHEMFET, the appropriate background information will...during the past decade for detecting organophosphorus compounds, the chemically- sensitive thin films investigated in this thesis, and finally, the...reactivate the phosphorylated cholinesterase enzyme. Solid State Chemical Sensors During the past decade, a number of solid state chemical sensors have been

Salt flux synthesis of single and bimetallic carbide nanowires

NASA Astrophysics Data System (ADS)

Leonard, Brian M.; Waetzig, Gregory R.; Clouser, Dale A.; Schmuecker, Samantha M.; Harris, Daniel P.; Stacy, John M.; Duffee, Kyle D.; Wan, Cheng

2016-07-01

Metal carbide compounds have a broad range of interesting properties and are some of the hardest and highest melting point compounds known. However, their high melting points force very high reaction temperatures and thus limit the formation of high surface area nanomaterials. To avoid the extreme synthesis temperatures commonly associated with these materials, a new salt flux technique has been employed to reduce reaction temperatures and form these materials in the nanometer regime. Additionally, the use of multiwall carbon nanotubes as a reactant further reduces the diffusion distance and provides a template for the final carbide materials. The metal carbide compounds produced through this low temperature salt flux technique maintain the nanowire morphology of the carbon nanotubes but increase in size to ˜15-20 nm diameter due to the incorporation of metal in the carbon lattice. These nano-carbides not only have nanowire like shape but also have much higher surface areas than traditionally prepared metal carbides. Finally, bimetallic carbides with composition control can be produced with this method by simply using two metal precursors in the reaction. This method provides the ability to produce nano sized metal carbide materials with size, morphology, and composition control and will allow for these compounds to be synthesized and studied in a whole new size and temperature regime.

Development of a high-throughput method to evaluate the impact of inhibitory compounds from lignocellulosic hydrolysates on the growth of Zymomonas mobilis.

PubMed

Franden, Mary Ann; Pienkos, Philip T; Zhang, Min

2009-12-01

Overcoming the effects of hydrolysate toxicity towards ethanologens is a key technical barrier in the biochemical conversion process for biomass feedstocks to ethanol. Despite its importance, the complexity of the hydrolysate toxicity phenomena and the lack of systematic studies, analysis and tools surrounding this issue have blocked a full understanding of relationships involving toxic compounds in hydrolysates and their effects on ethanologen growth and fermentation. In this study, we developed a quantitative, high-throughput biological growth assay using an automated turbidometer to obtain detailed inhibitory kinetics for individual compounds present in lignocellulosic biomass hydrolysate. Information about prolonged lag time and final cell densities can also be obtained. The effects of furfural, hydroxymethylfurfural (HMF), acetate and ethanol on growth rate and final cell densities of Zymomonas mobilis 8b on glucose are presented. This method was also shown to be of value in toxicity studies of hydrolysate itself, despite the highly colored nature of this material. Using this approach, we can generate comprehensive inhibitory profiles with many individual compounds and develop models that predict and examine toxic effects in the complex mixture of hydrolysates, leading to the development of improved pretreatment and conditioning processes as well as fermentation organisms.

Combining structure-based pharmacophore modeling, virtual screening, and in silico ADMET analysis to discover novel tetrahydro-quinoline based pyruvate kinase isozyme M2 activators with antitumor activity

PubMed Central

Chen, Can; Wang, Ting; Wu, Fengbo; Huang, Wei; He, Gu; Ouyang, Liang; Xiang, Mingli; Peng, Cheng; Jiang, Qinglin

2014-01-01

Compared with normal differentiated cells, cancer cells upregulate the expression of pyruvate kinase isozyme M2 (PKM2) to support glycolytic intermediates for anabolic processes, including the synthesis of nucleic acids, amino acids, and lipids. In this study, a combination of the structure-based pharmacophore modeling and a hybrid protocol of virtual screening methods comprised of pharmacophore model-based virtual screening, docking-based virtual screening, and in silico ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis were used to retrieve novel PKM2 activators from commercially available chemical databases. Tetrahydroquinoline derivatives were identified as potential scaffolds of PKM2 activators. Thus, the hybrid virtual screening approach was applied to screen the focused tetrahydroquinoline derivatives embedded in the ZINC database. Six hit compounds were selected from the final hits and experimental studies were then performed. Compound 8 displayed a potent inhibitory effect on human lung cancer cells. Following treatment with Compound 8, cell viability, apoptosis, and reactive oxygen species (ROS) production were examined in A549 cells. Finally, we evaluated the effects of Compound 8 on mice xenograft tumor models in vivo. These results may provide important information for further research on novel PKM2 activators as antitumor agents. PMID:25214764

THE BIOSYNTHESIS OF TERTHIENYL. Progress Report , June 7, 1961-February 15, 1962

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

None

The preparation of terthienyl, degradation reactions of terthienyl, isolation of terthienyl from marigold blooms and roots, conditions for growing marigold plants in the laboratory, and the isolation of three unknown compounds of possible relation to terthienyl from marigolds are discussed. (M.C.G.)

Straight A's: Public Education Policy and Progress. Volume 11, Number 8

ERIC Educational Resources Information Center

Amos, Jason, Ed.

2011-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) Last Cut Is the Deepest: Final FY 2011 Spending Agreement Cuts Spending by Nearly $40 Billion, Includes More Cuts for Education…

A Visualization System for Predicting Learning Activities Using State Transition Graphs

ERIC Educational Resources Information Center

Okubo, Fumiya; Shimada, Atsushi; Taniguchi, Yuta

2017-01-01

In this paper, we present a system for visualizing learning logs of a course in progress together with predictions of learning activities of the following week and the final grades of students by state transition graphs. Data are collected from 236 students attending the course in progress and from 209 students attending the past course for…

STAGE-DEPENDENCE, SEASONAL CHANGES AND EFFECTS OF CADMIUM ON CELL CYCLE AND APOPTOTIC ACTIVITIES DURING THE SPERMATOGENIC PROGRESSION IN THE DOGFISH SHARK (SQUALUS ACANTHIAS). (R825434)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Jet Crackle

DTIC Science & Technology

2015-06-23

DISTRIBUTION/AVAILABILITY STATEMENT DISTRIBUTION A 13. SUPPLEMENTARY NOTES 14. ABSTRACT Fighter jets and other aircraft with high specific thrust engines...interim, memorandum, master’s thesis , progress, quarterly, research, special, group study, etc. 3. DATES COVERED. Indicate the time during which the...State the type of report, such as final, technical, interim, memorandum, master’s thesis , progress, quarterly, research, special, group study, etc

[Research progress of thermal control system for extravehicular activity space suit].

PubMed

Wu, Z Q; Shen, L P; Yuan, X G

1999-08-01

New research progress of thermal control system for oversea Extravehicular Activity (EVA) space suit is presented. Characteristics of several thermal control systems are analyzed in detail. Some research tendencies and problems are discussed, which are worthwhile to be specially noted. Finally, author's opinion about thermal control system in the future is put forward.

Reading Achievement in Disadvantaged Children as a Consequence of Non Verbal Perceptual Training. Final Technical Progress Report.

ERIC Educational Resources Information Center

Elkind, David; Deblinger, Jo Ann

The theoretical orientation based on perceptual development, proposed by Piaget in 1961, is the starting point of this investigation. According to Piaget, the perception of the young child is "centered" on dominant aspects of the field. With maturity, perception becomes "decentered" and progressively freed from the field. The…

Straight A's: Public Education Policy and Progress. Volume 9, Number 23

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2009

2009-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) Two Omnibus Bills and a Partridge in a Pear Tree?: Final Vote on Education Appropriations Bill Could Come Before…

Bio-inspired hemispherical compound eye camera

NASA Astrophysics Data System (ADS)

Xiao, Jianliang; Song, Young Min; Xie, Yizhu; Malyarchuk, Viktor; Jung, Inhwa; Choi, Ki-Joong; Liu, Zhuangjian; Park, Hyunsung; Lu, Chaofeng; Kim, Rak-Hwan; Li, Rui; Crozier, Kenneth B.; Huang, Yonggang; Rogers, John A.

2014-03-01

Compound eyes in arthropods demonstrate distinct imaging characteristics from human eyes, with wide angle field of view, low aberrations, high acuity to motion and infinite depth of field. Artificial imaging systems with similar geometries and properties are of great interest for many applications. However, the challenges in building such systems with hemispherical, compound apposition layouts cannot be met through established planar sensor technologies and conventional optics. We present our recent progress in combining optics, materials, mechanics and integration schemes to build fully functional artificial compound eye cameras. Nearly full hemispherical shapes (about 160 degrees) with densely packed artificial ommatidia were realized. The number of ommatidia (180) is comparable to those of the eyes of fire ants and bark beetles. The devices combine elastomeric compound optical elements with deformable arrays of thin silicon photodetectors, which were fabricated in the planar geometries and then integrated and elastically transformed to hemispherical shapes. Imaging results and quantitative ray-tracing-based simulations illustrate key features of operation. These general strategies seem to be applicable to other compound eye devices, such as those inspired by moths and lacewings (refracting superposition eyes), lobster and shrimp (reflecting superposition eyes), and houseflies (neural superposition eyes).

In silico-based combinatorial pharmacophore modelling and docking studies of GSK-3β and GK inhibitors of Hippophae.

PubMed

Middha, Sushil Kumar; Goyal, Arvind Kumar; Faizan, Syed Ahmed; Sanghamitra, Nethramurthy; Basistha, Bharat Chandra; Usha, Talambedu

2013-11-01

Type 2 diabetes is an inevitably progressive disease, with irreversible beta cell failure. Glycogen synthase kinase and Glukokinase, two important enzymes with diverse biological actions in carbohydrate metabolism, are promising targets for developing novel antidiabetic drugs. A combinatorial structure-based molecular docking and pharmacophore modelling study was performed with the compounds of Hippophae salicifolia and H. rhamnoides as inhibitors. Docking with Discovery Studio 3.5 revealed that two compounds from H. salicifolia, viz Lutein D and an analogue of Zeaxanthin, and two compounds from H. rhamnoides, viz Isorhamnetin-3-rhamnoside and Isorhamnetin-7-glucoside, bind significantly to the GSK-3 beta receptor and play a role in its inhibition; whereas in the case of Glucokinase, only one compound from both the plants, i.e. vitamin C, had good binding characteristics capable of activation. The results help to understand the type of interactions that occur between the ligands and the receptors. Toxicity predictions revealed that none of the compounds had hepatotoxic effects and had good absorption as well as solubility characteristics. The compounds did not possess plasma protein-binding, crossing blood-brain barrier ability. Further, in vivo and in vitro studies need to be performed to prove that these compounds can be used effectively as antidiabetic drugs.

Antimalarial compounds in Phase II clinical development.

PubMed

Held, Jana; Jeyaraj, Sankarganesh; Kreidenweiss, Andrea

2015-03-01

Malaria is a major health problem in endemic countries and chemotherapy remains the most important tool in combating it. Treatment options are limited and essentially rely on a single drug class - the artemisinins. Efforts are ongoing to restrict the evolving threat of artemisinin resistance but declining sensitivity has been reported. Fueled by the ambitious aim of malaria eradication, novel antimalarial compounds, with improved properties, are now in the progressive phase of drug development. Herein, the authors describe antimalarial compounds currently in Phase II clinical development and present the results of these investigations. Thanks to recent efforts, a number of promising antimalarial compounds are now in the pipeline. First safety data have been generated for all of these candidates, although their efficacy as antimalarials is still unclear for most of them. Of particular note are KAE609, KAF156 and DSM265, which are of chemical scaffolds new to malaria chemotherapy and would truly diversify antimalarial options. Apart from SAR97276, which also has a novel chemical scaffold that has had its development stopped, all other compounds in the pipeline belong to already known substance classes, which have been chemically modified. At this moment in time, there is not one standout compound that will revolutionize malaria treatment but several compounds that will add to its control in the future.

Improved BM212 MmpL3 Inhibitor Analogue Shows Efficacy in Acute Murine Model of Tuberculosis Infection

PubMed Central

Alfonso, Salvatore; Cocozza, Martina; Porretta, Giulio Cesare; Ballell, Lluís; Rullas, Joaquin; Ortega, Fátima; De Logu, Alessandro; Agus, Emanuela; La Rosa, Valentina; Pasca, Maria Rosalia; De Rossi, Edda; Wae, Baojie; Franzblau, Scott G.; Manetti, Fabrizio; Botta, Maurizio; Biava, Mariangela

2013-01-01

1,5-Diphenyl pyrroles were previously identified as a class of compounds endowed with high in vitro efficacy against M. tuberculosis. To improve the physical chemical properties and drug-like parameters of this class of compounds, a medicinal chemistry effort was undertaken. By selecting the optimal substitution patterns for the phenyl rings at N1 and C5 and by replacing the thiomorpholine moiety with a morpholine one, a new series of compounds was produced. The replacement of the sulfur with oxygen gave compounds with lower lipophilicity and improved in vitro microsomal stability. Moreover, since the parent compound of this family has been shown to target MmpL3, mycobacterial mutants resistant to two compounds have been isolated and characterized by sequencing the mmpL3 gene; all the mutants showed point mutations in this gene. The best compound identified to date was progressed to dose-response studies in an acute murine TB infection model. The resulting ED99 of 49 mg/Kg is within the range of commonly employed tuberculosis drugs, demonstrating the potential of this chemical series. The in vitro and in vivo target validation evidence presented here adds further weight to MmpL3 as a druggable target of interest for anti-tubercular drug discovery. PMID:23437287

Placental ABC Transporters: Biological Impact and Pharmaceutical Significance.

PubMed

Joshi, Anand A; Vaidya, Soniya S; St-Pierre, Marie V; Mikheev, Andrei M; Desino, Kelly E; Nyandege, Abner N; Audus, Kenneth L; Unadkat, Jashvant D; Gerk, Phillip M

2016-12-01

The human placenta fulfills a variety of essential functions during prenatal life. Several ABC transporters are expressed in the human placenta, where they play a role in the transport of endogenous compounds and may protect the fetus from exogenous compounds such as therapeutic agents, drugs of abuse, and other xenobiotics. To date, considerable progress has been made toward understanding ABC transporters in the placenta. Recent studies on the expression and functional activities are discussed. This review discusses the placental expression and functional roles of several members of ABC transporter subfamilies B, C, and G including MDR1/P-glycoprotein, the MRPs, and BCRP, respectively. Since placental ABC transporters modulate fetal exposure to various compounds, an understanding of their functional and regulatory mechanisms will lead to more optimal medication use when necessary in pregnancy.

Placental ABC Transporters: Biological Impact and Pharmaceutical Significance

PubMed Central

Joshi, Anand A.; Vaidya, Soniya S.; St-Pierre, Marie V.; Mikheev, Andrei M.; Desino, Kelly E.; Nyandege, Abner N.; Audus, Kenneth L.; Unadkat, Jashvant D.; Gerk, Phillip M.

2017-01-01

The human placenta fulfills a variety of essential functions during prenatal life. Several ABC transporters are expressed in the human placenta, where they play a role in the transport of endogenous compounds and may protect the fetus from exogenous compounds such as therapeutic agents, drugs of abuse, and other xenobiotics. To date, considerable progress has been made toward understanding ABC transporters in the placenta. Recent studies on the expression and functional activities are discussed. This review discusses the placental expression and functional roles of several members of ABC transporter subfamilies B, C, and G including MDR1/P-glycoprotein, the MRPs, and BCRP, respectively. Since placental ABC transporters modulate fetal exposure to various compounds, an understanding of their functional and regulatory mechanisms will lead to more optimal medication use when necessary in pregnancy. PMID:27644937

Intra-oral adsorption and release of aroma compounds following in-mouth wine exposure.

PubMed

Esteban-Fernández, Adelaida; Rocha-Alcubilla, Nuria; Muñoz-González, Carolina; Moreno-Arribas, María Victoria; Pozo-Bayón, María Ángeles

2016-08-15

Wine "after-odour" defined as the long lasting aroma perception that remains after wine swallowing is an outstanding characteristic in terms of wine quality but a relatively unstudied phenomenon. Among the different parameters that might affect wine after-odour, the adsorption of odorants by the oral mucosa could be important but has been little explored. In this work, the impact of the chemical characteristics of aroma compounds on intra-oral adsorption was assessed by an in vivo approach that determined the amounts of odorants remaining in expectorated wine samples. In addition, the subsequent aroma release after in-mouth wine exposure was studied by means of intra-oral SPME/GC-MS using three different panellists. Oral adsorption of the aroma compounds added to the wines ranged from 6% to 43%, depending on their physicochemical characteristics. A progressive intra-oral aroma decrease at different decay rates depending on compound type and panellist was also found. The strength of the aroma-oral mucosa interactions seems to explain these results more than the amount of compound adsorbed by the oral mucosa. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pyridine-pyrimidine amides that prevent HGF-induced epithelial scattering by two distinct mechanisms.

PubMed

Siddiqui-Jain, Adam; Hoj, Jacob P; Hargiss, J Blade; Hoj, Taylor H; Payne, Carter J; Ritchie, Collin A; Herron, Steven R; Quinn, Colette; Schuler, Jeffrey T; Hansen, Marc D H

2017-09-01

Stimulation of cultured epithelial cells with scatter factor/hepatocyte growth factor (HGF) results in individual cells detaching and assuming a migratory and invasive phenotype. Epithelial scattering recapitulates cancer progression and studies have implicated HGF signaling as a driver of cancer metastasis. Inhibitors of HGF signaling have been proposed to act as anti-cancer agents. We previously screened a small molecule library for compounds that block HGF-induced epithelial scattering. Most hits identified in this screen exhibit anti-mitotic properties. Here we assess the biological mechanism of a compound that blocks HGF-induced scattering with limited anti-mitotic activity. Analogs of this compound have one of two distinct activities: inhibiting either cell migration or cell proliferation with cell cycle arrest in G2/M. Each activity bears unique structure-activity relationships. The mechanism of action of anti-mitotic compounds is by inhibition of microtubule polymerization; these compounds entropically and enthalpically bind tubulin in the colchicine binding site, generating a conformational change in the tubulin dimer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Experimental Realisation of Elusive Multiple-bonded Aluminium Compounds: A New Horizon in the Aluminium Chemistry.

PubMed

Inoue, Shigeyoshi; Bag, Prasenjit; Weetman, Catherine

2018-05-23

Synthesis and isolation of stable main group compounds featuring multiple bonds has been of keen interest for the last several decades. Multiply bonded complexes were obtained using sterically demanding substituents that provide kinetic and thermodynamic stability. Many of these compounds have unusual structural and electronic properties that challenges the classical concept of covalent multiple bonding. In contrast, analogous aluminium compounds are scarce in spite of its high natural abundance. The parent dialumene (Al2H2) has been calculated to be extremely weak, thus making Al multiple bonds a challenging synthetic target. This review provides an overview of these recent advances in the cutting edge synthetic approaches used to obtain aluminium homo- and heterodiatomic multiply bonded complexes. Additionally, the reactivity of these novel compounds towards various small molecules and reagents will be discussed herein. This review provides an overview on the current progress in aluminium multiple bond chemistry and the careful ligand design required to stabilise these reactive species. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bivalent ligands incorporating curcumin and diosgenin as multifunctional compounds against Alzheimer's disease.

PubMed

Chojnacki, Jeremy E; Liu, Kai; Saathoff, John M; Zhang, Shijun

2015-11-15

In an effort to combat the multifaceted nature of Alzheimer's disease (AD) progression, a series of multifunctional, bivalent compounds containing curcumin and diosgenin were designed, synthesized, and biologically characterized. Screening results in MC65 neuroblastoma cells established that compound 38 with a spacer length of 17 atoms exhibited the highest protective potency with an EC50 of 111.7 ± 9.0 nM. A reduction in protective activity was observed as spacer length was increased up to 28 atoms and there is a clear structural preference for attachment to the methylene carbon between the two carbonyl moieties of curcumin. Further study suggested that antioxidative ability and inhibitory effects on amyloid-β oligomer (AβO) formation may contribute to the neuroprotective outcomes. Additionally, compound 38 was found to bind directly to Aβ, similar to curcumin, but did not form complexes with the common biometals Cu, Fe, and Zn. Altogether, these results give strong evidence to support the bivalent design strategy in developing novel compounds with multifunctional ability for the treatment of AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tom Green County Library Literacy Project. Final Performance Report.

ERIC Educational Resources Information Center

Vavricka, D. Karen

The final report of the Tom Green Country Library System (Texas) literacy project details progress toward achievement of 11 objectives. Objectives of the literacy outreach program were to: (1) increase Hispanic enrollment; (2) increase Black enrollment; (3) provide free child care for 4 students to attend 50 tutoring sessions; (4) provide…

TREMATODES IN SNAILS NEAR RACCOON LATRINES SUGGEST A FINAL HOST ROLE FOR THIS MAMMAL IN CALIFORNIA SALT MARSHES. (R828676C001)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

George A. Olah, Carbocation and Hydrocarbon Chemistry

Science.gov Websites

. Final Technical Report. [HF:BF{sub 2}/H{sub 2}] , DOE Technical Report, 1980 Superacid Catalyzed Coal Conversion Chemistry. 1st and 2nd Quarterly Technical Progress Reports, September 1, 1983-March 30, 1984 , DOE Technical Report, 1984 Superacid Catalyzed Coal Conversion Chemistry. Final Technical Report

THE DEVELOPMENT AND PRESENTATION OF FOUR COLLEGE COURSES BY COMPUTER TELEPROCESSING. FINAL REPORT.

ERIC Educational Resources Information Center

MITZEL, HAROLD E.

THIS IS A FINAL REPORT ON THE DEVELOPMENT AND PRESENTATION OF FOUR COLLEGE COURSES BY COMPUTER TELEPROCESSING FROM APRIL 1964 TO JUNE 1967. IT OUTLINES THE PROGRESS MADE TOWARDS THE PREPARATION, DEVELOPMENT, AND EVALUATION OF MATERIALS FOR COMPUTER PRESENTATION OF COURSES IN AUDIOLOGY, MANAGEMENT ACCOUNTING, ENGINEERING ECONOMICS, AND MODERN…

40 CFR 62.14565 - How do I comply with the increment of progress for achieving final compliance?

Code of Federal Regulations, 2013 CFR

2013-07-01

... DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Compliance Schedule and... complete retrofit construction of control devices, as specified in the final control plan, so that, when...

New antimuscarinic agents for improved treatment of poisoning by cholinesterase inhibitors. Annual progress report No. 1, 1 November 1982-31 October 1983

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

Stubbins, J.F.

The object of this project is to find a more effective antimuscarinic agent than atropine for use as an antidote for poisoning by organophosphate cholinesterase inhibitors. To start this search, 22 structurally-diverse antimuscarinic agents have been selected for initial testing. These compounds are to be evaluated for peripheral and central antimuscarinic activity in a variety of in vitro and in vivo tests in addition to determining their effectiveness as antidotes (in combination with an oxime reactivator) for poisoning by soman. Fifteen of the compounds have now been evaluated for ability to block acetylcholine-induced contractions in guinea pig intestinal smooth musclemore » compared to atropine. Ability to displace radiolabeled quinuclidinyl benzilate from muscarinic receptors of mouse brain homogenate has been determined for atropine, scopolamine and 19 of the compounds. Several of these compounds have a relatively stronger affinity for brain than for intestinal muscarinic receptors. Atropine, scopolamine and 12 of the compounds have also been examined as inhibitors of tremors induced by oxotremorine in mice. Two of the compounds are much more potent than atropine. None of the compounds have been tested as yet as antidotes for soman poisoning. Samples of the test compounds are being sent to the Medical Research Institute of Chemical Defense for evaluation of this property.« less

PFBC HGCU Test Facility. Technical progress report No. 24, Third quarter, CY 1995

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

NONE

This is the twenty-fourth and final Technical Progress Report submitted to the Department of Energy (DOE) in connection with the cooperative agreement between the DOE and Ohio Power Company for the Tidd PFBC Hot Gas Clean Up Test Facility. This report covers the work completed during the Third Quarter of CY 1995. All activity this quarter was directed toward the completion of the program final report. A draft copy of the final report was forwarded to DOE during this quarter, and DOE submitted their comments on the report to AEPSC. DOE requested that Westinghouse write an appendix to the reportmore » covering the performance of the fail-safe regenerator devices during Tad operation, and Westinghouse subsequently prepared the appendix. Additional DOE comments were incorporated into the report, and it will be issued in camera-ready form by the end of October, 1995, which is the program end date. Appendix 1 presents the results of filter candle posttest examination by Westinghouse performed on selected filter candles following final shutdown of the system.« less

Cholesterol - a biological compound as a building block in bionanotechnology

NASA Astrophysics Data System (ADS)

Hosta-Rigau, Leticia; Zhang, Yan; Teo, Boon M.; Postma, Almar; Städler, Brigitte

2012-12-01

Cholesterol is a molecule with many tasks in nature but also a long history in science. This feature article highlights the contribution of this small compound to bionanotechnology. We discuss relevant chemical aspects in this context followed by an overview of its self-assembly capabilities both as a free molecule and when conjugated to a polymer. Further, cholesterol in the context of liposomes is reviewed and its impact ranging from biosensing to drug delivery is outlined. Cholesterol is and will be an indispensable player in bionanotechnology, contributing to the progress of this potent field of research.

The contentious nature of soil organic matter.

PubMed

Lehmann, Johannes; Kleber, Markus

2015-12-03

The exchange of nutrients, energy and carbon between soil organic matter, the soil environment, aquatic systems and the atmosphere is important for agricultural productivity, water quality and climate. Long-standing theory suggests that soil organic matter is composed of inherently stable and chemically unique compounds. Here we argue that the available evidence does not support the formation of large-molecular-size and persistent 'humic substances' in soils. Instead, soil organic matter is a continuum of progressively decomposing organic compounds. We discuss implications of this view of the nature of soil organic matter for aquatic health, soil carbon-climate interactions and land management.

Diamidines as antitrypanosomal, antileishmanial and antimalarial agents.

PubMed

Werbovetz, Karl

2006-02-01

Diamidine-containing compounds have a long history of use in the treatment of African trypanosomiasis and leishmaniasis. The discovery that diamidine prodrugs possess in vivo antimicrobial activity when administered orally has led to a renewed interest in this class of compounds for the treatment of parasitic infections. In this review, the selectivity of diamidines against trypanosomes, Leishmania and Plasmodium is rationalized through mechanism-of-action studies. An overview of the antiprotozoal activities of newer diamidines and diamidine prodrugs is also presented, along with a summary of the progress made toward the clinical development of new diamidines for use against these parasitic diseases.

Structure Diversity, Synthesis, and Biological Activity of Cyathane Diterpenoids in Higher Fungi.

PubMed

Tang, Hao-Yu; Yin, Xia; Zhang, Cheng-Chen; Jia, Qian; Gao, Jin-Ming

2015-01-01

Cyathane diterpenoids, occurring exclusively in higher basidiomycete (mushrooms), represent a structurally diverse class of natural products based on a characteristic 5-6-7 tricyclic carbon scaffold, including 105 members reported to date. These compounds show a diverse range of biological activities, such as antimicrobial, anti-MRSA, agonistic toward the kappa-opioid receptor, antiinflammatory, anti-proliferative and nerve growth factor (NGF)-like properties. The present review focuses on the structure diversity, structure elucidation and biological studies of these compounds, including mechanisms of actions and structure-activity relationships (SARs). In addition, new progress in chemical synthesis of cyathane diterpenoids is discussed.

[Separation and purification of the components in Trachelospermum jasminoides by two dimensional hydrophilic interaction liquid chromatography- reversed-phase liquid chromatography].

PubMed

Jia, Youmei; Cai, Jianfeng; Xin, Huaxia; Feng, Jiatao; Fu, Yanhui; Fu, Qing; Jin, Yu

2017-06-08

A preparative two dimensional hydrophilic interaction liquid chromatography/reversed-phase liquid chromatography (Pre-2D-HILIC/RPLC) method was established to separate and purify the components in Trachelospermum jasminoides . The pigments and strongly polar components were removed from the crude extract after the active carbon decolorization and solid phase extraction processes. A Click XIon column (250 mm×20 mm, 10 μm) was selected as stationary phase and water-acetonitrile as mobile phases in the first dimensional HILIC. Finally, 15 fractions were collected under UV-triggered mode. In the second dimensional RPLC, a C18 column (250 mm×20 mm, 5 μm) was selected and water-acetonitrile was used as mobile phases. As a result, 14 compounds with high purity were obtained, which were further identified by mass spectrometry (MS) and nuclear magnetic resonance (NMR). Finally, 11 lignan compounds and three flavonoid compounds were obtained. The method has a good orthogonality, and can improve the resolution and the peak capacity. It is significant for the separation of complex components from Trachelospermum jasminoides .

Improved heterologous production of the nonribosomal peptide-polyketide siderophore yersiniabactin through metabolic engineering and induction optimization.

PubMed

Ahmadi, Mahmoud Kamal; Pfeifer, Blaine A

2016-11-01

Biosynthesis of complex natural products like polyketides and nonribosomal peptides using Escherichia coli as a heterologous host provides an opportunity to access these molecules. The value in doing so stems from the fact that many compounds hold some therapeutic or other beneficial property and their original production hosts are intractable for a variety of reasons. In this work, metabolic engineering and induction variable optimization were used to increase production of the polyketide-nonribosomal peptide compound yersiniabactin, a siderophore that has been utilized to selectively remove metals from various solid and aqueous samples. Specifically, several precursor substrate support pathways were altered through gene expression and exogenous supplementation in order to boost production of the final compound. The gene expression induction process was also analyzed to identify the temperatures and inducer concentrations resulting in highest final production levels. When combined, yersiniabactin production was extended to ∼175 mg L -1 . © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1412-1417, 2016. © 2016 American Institute of Chemical Engineers.

Green remediation. Tool for safe and sustainable environment: a review

NASA Astrophysics Data System (ADS)

Singh, Mamta; Pant, Gaurav; Hossain, Kaizar; Bhatia, A. K.

2017-10-01

Nowadays, the bioremediation of toxic pollutants is a subject of interest in terms of health issues and environmental cleaning. In the present review, an eco-friendly, cost-effective approach is discussed for the detoxification of environmental pollutants by the means of natural purifier, i.e., blue-green algae over the conventional methods. Industrial wastes having toxic pollutants are not able to eliminate completely by existing the conventional techniques; in fact, these methods can only change their form rather than the entire degradation. These pollutants have an adverse effect on aquatic life, such as fauna and flora, and finally harm human life directly or indirectly. Cyanobacterial approach for the removal of this contaminant is an efficient tool for sustainable development and pollution control. Cyanobacteria are the primary consumers of food chain which absorbed complex toxic compounds from environments and convert them to simple nontoxic compounds which finally protect higher food chain consumer and eliminate risk of pollution. In addition, these organisms have capability to solve secondary pollution, as they can remediate radioactive compound, petroleum waste and degrade toxins from pesticides.

Preparation and Quality Control of the [153Sm]-Samarium Maltolate Complex as a Lanthanide Mobilization Product in Rats

PubMed Central

Naseri, Zohreh; Hakimi, Amir; Jalilian, Amir R.; Nemati Kharat, Ali; Bahrami-Samani, Ali; Ghannadi-Maragheh, Mohammad

2011-01-01

Development of lanthanide detoxification agents and protocols is of great importance in management of overdoses. Due to safety of maltol as a detoxifying agent in metal overloads, it can be used as a lanthanide detoxifying agent. In order to demonstrate the biodistribution of final complex, [153Sm]-samarium maltolate was prepared using Sm-153 chloride (radiochemical purity >99.9%; ITLC and specific activity). The stability of the labeled compound was determined in the final solution up to 24h as well as the partition coefficient. Biodistribution studies of Sm-153 chloride, [153Sm]-samarium maltolate were carried out in wild-type rats comparing the critical organ uptakes. Comparative study for Sm3+ cation and the labeled compound was conducted up to 48 h, demonstrating a more rapid wash out for the labeled compound. The effective and biological half lives of 2.3 h and 2.46h were calculated for the complex. The data suggest the detoxification property of maltol formulation for lanthanide overdoses. PMID:21773065

A combination of 2D similarity search, pharmacophore, and molecular docking techniques for the identification of vascular endothelial growth factor receptor-2 inhibitors.

PubMed

Ai, Guanhua; Tian, Caiping; Deng, Dawei; Fida, Guissi; Chen, Haiyan; Ma, Yuxiang; Ding, Li; Gu, Yueqing

2015-04-01

The human vascular endothelial growth factor receptor-2 (VEGFR-2) has been an attractive target for the inhibition of angiogenesis. In the current study, we used a hybrid protocol of virtual screening methods to retrieve new VEGFR-2 inhibitors from the Zinc-Specs Database (441 574 compounds). The hybrid protocol included the initial screening of candidates by comparing the 2D similarity to five reported top active inhibitors of 13 VEGFR-2 X-ray crystallography structures, followed by the pharmacophore modeling of virtual screening on the basis of receptor-ligand interactions and further narrowing by LibDOCK to obtain the final hits. Two compounds (AN-919/41439526 and AK-968/40939851) with a high libscore were selected as the final hits for a subsequent cell cytotoxicity study. The two compounds screened exerted significant inhibitory effects on the proliferation of cancer cells (U87 and MCF-7). The results indicated that the hybrid procedure is an effective approach for screening specific receptor inhibitors.

Methods to assess the effects of environmental chemicals on the brain-pituitary-gonad axis of the reproductive system

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

Magliulo-Cepriano, L.; Schreibman, M.P.

1999-07-01

In all vertebrates, the neuroendocrine system serves as the primary and essential link between the external and internal environments and a multitude of physiological systems, including the reproductive system. In response to changes in the environment and fluctuations in levels of circulating humoral agents, the neuroendocrine system is able to reverse, maintain or advance physiological events. Endocrine disrupting compounds are believed to wreak havoc on reproduction and development by interfering in the normal flow of information along the brain-pituitary-gonad axis. While the final effects of these compounds may be easily determined in a number of species, utilization of non-traditional researchmore » animals, such as some fishes in which the pattern of information flow along the brain-pituitary-gonad axis has been meticulously detailed and documented, will provide excellent and novel means of elucidating not only the final effects but the cytological, histological and systemic mechanisms of action of these endocrine disruptors. This report presents methods of assessing the effects of endocrine disrupting compounds on a variety of physiological and morphological parameters in fishes.« less

Experimental and Theoretical Studies of Atmosphereic Inorganic Chlorine Chemistry

NASA Technical Reports Server (NTRS)

Sander, Stanley P.; Friedl, Randall R.

1993-01-01

Over the last five years substantial progress has been made in defining the realm of new chlorine chemistry in the polar stratosphere. Application of existing experimental techniques to potentially important chlorine-containing compounds has yielded quantitative kinetic and spectroscopic data as well as qualitative mechanistic insights into the relevant reactions.

A STATISTICAL SURVEY OF DIOXIN-LIKE COMPOUNDS IN U.S. BEEF: A PROGRESS REPORT

EPA Science Inventory

The USEPA and the USDA completed the first statistically designed survey of the occurrence and concentration of dibenzo-p-dioxins (CDDs), dibenzofurans (CDFs), and coplanar polychlorinated biphenyls (PCBs) in the fat of beef animals raised for human consumption in the United Stat...

Multiheteromacrocycles that Complex Metal Ions. Fourth Progress Report, 1 May 1977 -- 30 April 1978

DOE R&D Accomplishments Database

Cram, D. J.

1978-01-15

Results are reported in a program to design, synthesize, and evaluate polycyclic host organic compounds for their abilities to complex and lipophilize guest metal ions. Work during the reporting period was devoted to synthesis and study of cyclohexametaphenylenes and cyclic phosphine oxides. (JRD)

[Reviews on antiviral activity of chemical constituents from plants].

PubMed

Yang, Xian-Feng; Wang, Yu-Li; Xu, Wei-Ren

2008-01-01

This paper reviewed the progress in researches on antiviral activity of chemical constituents from plants in recent years, the antiviral activity and mechanism of action of flavonoids, alkaloids, terpenoids, coumarins and polysaccharoses were sammarszed, provided new leading compound for antivirus new drugs from the plares in prospect.

Development of a Conceptual Model of Disease Progression for Use in Economic Modeling of Chronic Obstructive Pulmonary Disease.

PubMed

Tabberer, Maggie; Gonzalez-McQuire, Sebastian; Muellerova, Hana; Briggs, Andrew H; Rutten-van Mölken, Maureen P M H; Chambers, Mike; Lomas, David A

2017-05-01

To develop and validate a new conceptual model (CM) of chronic obstructive pulmonary disease (COPD) for use in disease progression and economic modeling. The CM identifies and describes qualitative associations between disease attributes, progression and outcomes. A literature review was performed to identify any published CMs or literature reporting the impact and association of COPD disease attributes with outcomes. After critical analysis of the literature, a Steering Group of experts from the disciplines of health economics, epidemiology and clinical medicine was convened to develop a draft CM, which was refined using a Delphi process. The refined CM was validated by testing for associations between attributes using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). Disease progression attributes included in the final CM were history and occurrence of exacerbations, lung function, exercise capacity, signs and symptoms (cough, sputum, dyspnea), cardiovascular disease comorbidities, 'other' comorbidities (including depression), body composition (body mass index), fibrinogen as a biomarker, smoking and demographic characteristics (age, gender). Mortality and health-related quality of life were determined to be the most relevant final outcome measures for this model, intended to be the foundation of an economic model of COPD. The CM is being used as the foundation for developing a new COPD model of disease progression and to provide a framework for the analysis of patient-level data. The CM is available as a reference for the implementation of further disease progression and economic models.

A review on advanced oxidation processes for the removal of taste and odor compounds from aqueous media.

PubMed

Antonopoulou, M; Evgenidou, E; Lambropoulou, D; Konstantinou, I

2014-04-15

In view of the global concern about the occurrence of taste and odor (T&O) compounds in waters for drinking water supply and the necessity for the development of more innovative and efficient technologies for water treatment and depuration, the focus of this study is to provide a state of the art overview on current knowledge for the application of advanced oxidation technologies for the treatment of T&O compounds in aquatic media. The most representative and newly emerging compounds belonging to the major groups of T&O compounds, such as geosmin, methylisoborneol, benzothiazoles, mercaptans and sulfides as well as aromatic and other miscellaneous T&O compounds, are included in the systematic overview. The current data has been compiled and extensively discussed in terms of the degree of degradation, reaction kinetics, effect of operational parameters and water quality, identity of intermediate and final products and possible transformation pathways. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of low molecular weight compounds by MALDI-FTICR-MS.

PubMed

Wang, Hao-Yang; Chu, Xu; Zhao, Zhi-Xiong; He, Xiao-Shuang; Guo, Yin-Long

2011-05-15

This review focuses on recent applications of matrix-assisted laser desorption ionization-Fourier-transform ion cyclotron resonance mass spectrometry (MALDI-FTICR-MS) in qualitative and quantitative analysis of low molecular weight compounds. The scope of the work includes amino acids, small peptides, mono and oligosaccharides, lipids, metabolic compounds, small molecule phytochemicals from medicinal herbs and even the volatile organic compounds from tobacco. We discuss both direct analysis and analysis following derivatization. In addition we review sample preparation strategies to reduce interferences in the low m/z range and to improve sensitivities by derivatization with charge tags. We also present coupling of head space techniques with MALDI-FTICR-MS. Furthermore, omics analyses based on MALDI-FTICR-MS were also discussed, including proteomics, metabolomics and lipidomics, as well as the relative MS imaging for bio-active low molecular weight compounds. Finally, we discussed the investigations on dissociation/rearrangement processes of low molecular weight compounds by MALDI-FTICR-MS. Copyright © 2011 Elsevier B.V. All rights reserved.

Marine Pharmacology in 2012-2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

PubMed

Mayer, Alejandro M S; Rodríguez, Abimael D; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

2017-08-29

The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998-2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012-2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories.

Phenolic compounds from Byrsonima crassifolia L. bark: phytochemical investigation and quantitative analysis by LC-ESI MS/MS.

PubMed

Maldini, Mariateresa; Montoro, Paola; Pizza, Cosimo

2011-08-25

Phytochemical investigation of the methanolic extract of Byrsonima crassifolia's bark led to the isolation of 8 known phenolic compounds 5-O-galloylquinic acid, 3-O-galloylquinic acid, 3,4-di-O-galloylquinic acid, 3,5-di-O-galloylquinic acid, 3,4,5-tri-O-galloylquinic acid, (+)-epicatechin-3-gallate along with (+)-catechin and (+)-epicatechin. Due to their biological value, in the present study, a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, working in multiple reaction monitoring (MRM) mode, has been developed to quantify these compounds. B. crassifolia bark resulted in a rich source of phenolic compounds and particularly of galloyl derivates. The proposed analytical method is promising to be applied to other galloyl derivatives to quantify these bioactive compounds in raw material and final products. Copyright © 2011 Elsevier B.V. All rights reserved.

Quinoxaline-based inhibitors of Ebola and Marburg VP40 egress.

PubMed

Loughran, H Marie; Han, Ziying; Wrobel, Jay E; Decker, Sarah E; Ruthel, Gordon; Freedman, Bruce D; Harty, Ronald N; Reitz, Allen B

2016-08-01

We prepared a series of quinoxalin-2-mercapto-acetyl-urea analogs and evaluated them for their ability to inhibit viral egress in our Marburg and Ebola VP40 VLP budding assays in HEK293T cells. We also evaluated selected compounds in our bimolecular complementation assay (BiMC) to detect and visualize a Marburg mVP40-Nedd4 interaction in live mammalian cells. Antiviral activity was assessed for selected compounds using a live recombinant vesicular stomatitis virus (VSV) (M40 virus) that expresses the EBOV VP40 PPxY L-domain. Finally selected compounds were evaluated in several ADME assays to have an early assessment of their drug properties. Our compounds had low nM potency in these assays (e.g., compounds 21, 24, 26, 39), and had good human liver microsome stability, as well as little or no inhibition of P450 3A4. Copyright © 2016 Elsevier Ltd. All rights reserved.

Degradation of Energetic Compounds using Zero-Valent Iron (ZVI)

DTIC Science & Technology

2012-03-01

control number. 1. REPORT DATE MAR 2012 2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4 . TITLE AND SUBTITLE Degradation of Energetic...the column effluents were collected and passed through a 0.22- µm cellulose membrane filter (Millipore, Bedford, MA) for HPLC analysis. Degradation ...FINAL REPORT Degradation of Energetic Compounds Using Zero-Valent Iron (ZVI) ESTCP Project WP-200524 MARCH 2012 Byung J. Kim U.S

IRIS Toxicological Review of Beryllium and Compounds (2008 ...

EPA Pesticide Factsheets

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Beryllium that when finalized will appear on the Integrated Risk Information System (IRIS) database. An IRIS Toxicological Review of Beryllium and Compounds was published in 1988 and reassessed in 1998. The current draft (2007) only focuses on the cancer assessment and does not re-evaluate posted reference doses or reference concentrations.

Development Of An In Situ Passive Sampler For The Detection And Remediation of Explosive Compounds

DTIC Science & Technology

2016-06-07

FINAL REPORT Development of an In Situ Passive Sampler for the Detection and Remediation of Explosive Compounds SERDP Project ER-2539 MAY 2016...DATES COVERED (From - To) 4/24/15 – 12/1/2016 4. TITLE AND SUBTITLE Development of an In Situ Passive Sampler for the Detection and Remediation of...SUBJECT TERMS Passive samplers, Ethylene vinyl acetate, EVA sampler, Munitions, Monitoring, Remediation , Marine, Sediments 16. SECURITY

Multiparametric Phenotypic Screening System for Profiling Bioactive Compounds Using Human Fetal Hippocampal Neural Stem/Progenitor Cells.

PubMed

Tabata, Yoshikuni; Murai, Norio; Sasaki, Takeo; Taniguchi, Sachie; Suzuki, Shuichi; Yamazaki, Kazuto; Ito, Masashi

2015-10-01

Stem cell research has been progressing rapidly, contributing to regenerative biology and regenerative medicine. In this field, small-molecule compounds affecting stem cell proliferation/differentiation have been explored to understand stem cell biology and support regenerative medicine. In this study, we established a multiparametric screening system to detect bioactive compounds affecting the cell fate of human neural stem/progenitor cells (NSCs/NPCs), using human fetal hippocampal NSCs/NPCs, HIP-009 cells. We examined effects of 410 compounds, which were collected based on mechanisms of action (MOAs) and chemotypes, on HIP-009's cell fate (self-renewal, neuronal and astrocytic differentiation) and morphology by automated multiparametric assays and profiled induced cellular phenotypes. We found that this screening classified compounds with the same MOAs into subgroups according to additional pharmacological effects (e.g., mammalian target of rapamycin complex 1 [mTORC1] inhibitors and mTORC1/mTORC2 dual inhibitors among mTOR inhibitors). Moreover, it identified compounds that have off-target effects under matrix analyses of MOAs and structure similarities (e.g., neurotropic effects of amitriptyline among tri- and tetracyclic compounds). Therefore, this automated, medium-throughput and multiparametric screening system is useful for finding compounds that affect the cell fate of human NSCs/NPCs for supporting regenerative medicine and to fingerprint compounds based on human stem cells' multipotency, leading to understanding of stem cell biology. © 2015 Society for Laboratory Automation and Screening.

SEURAT-1 liver gold reference compounds: a mechanism-based review.

PubMed

Jennings, Paul; Schwarz, Michael; Landesmann, Brigitte; Maggioni, Silvia; Goumenou, Marina; Bower, David; Leonard, Martin O; Wiseman, Jeffrey S

2014-12-01

There is an urgent need for the development of alternative methods to replace animal testing for the prediction of repeat dose chemical toxicity. To address this need, the European Commission and Cosmetics Europe have jointly funded a research program for 'Safety Evaluation Ultimately Replacing Animal Testing.' The goal of this program was the development of in vitro cellular systems and associated computational capabilities for the prediction of hepatic, cardiac, renal, neuronal, muscle, and skin toxicities. An essential component of this effort is the choice of appropriate reference compounds that can be used in the development and validation of assays. In this review, we focus on the selection of reference compounds for liver pathologies in the broad categories of cytotoxicity and lipid disorders. Mitochondrial impairment, oxidative stress, and apoptosis are considered under the category of cytotoxicity, while steatosis, cholestasis, and phospholipidosis are considered under the category of lipid dysregulation. We focused on four compound classes capable of initiating such events, i.e., chemically reactive compounds, compounds with specific cellular targets, compounds that modulate lipid regulatory networks, and compounds that disrupt the plasma membrane. We describe the molecular mechanisms of these compounds and the cellular response networks which they elicit. This information will be helpful to both improve our understanding of mode of action and help in the selection of appropriate mechanistic biomarkers, allowing us to progress the development of animal-free models with improved predictivity to the human situation.

High-voltage positive electrode materials for lithium-ion batteries

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

Li, Wangda; Song, Bohang; Manthiram, Arumugam

The ever-growing demand for advanced rechargeable lithium-ion batteries in portable electronics and electric vehicles has spurred intensive research efforts over the past decade. The key to sustaining the progress in Li-ion batteries lies in the quest for safe, low-cost positive electrode (cathode) materials with desirable energy and power capabilities. One approach to boost the energy and power densities of batteries is to increase the output voltage while maintaining a high capacity, fast charge–discharge rate, and long service life. Here, this review gives an account of the various emerging high-voltage positive electrode materials that have the potential to satisfy these requirementsmore » either in the short or long term, including nickel-rich layered oxides, lithium-rich layered oxides, high-voltage spinel oxides, and high-voltage polyanionic compounds. The key barriers and the corresponding strategies for the practical viability of these cathode materials are discussed along with the optimization of electrolytes and other cell components, with a particular emphasis on recent advances in the literature. Finally, a concise perspective with respect to plausible strategies for future developments in the field is also provided.« less

Genotoxicity testing: progress and prospects for the next decade.

PubMed

Turkez, Hasan; Arslan, Mehmet E; Ozdemir, Ozlem

2017-10-01

Genotoxicity and mutagenicity analyses have a significant role in the identification of hazard effects of therapeutic drugs, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials for regulatory purposes. To evaluate mutagenicity or genotoxicity, different in vitro and in vivo methodologies exert various genotoxicological endpoints such as point mutations, changes in number and structure of chromosomes. Areas covered: This review covered the basics of genotoxicity and in vitro/in vivo methods for determining of genetic damages. The limitations that have arisen as a result of the common use of these methods were also discussed. Finally, the perspectives of further prospects on the use of genotoxicity testing and genotoxic mode of action were emphasized. Expert opinion: The solution of actual and practical problems of genetic toxicology is inarguably based on the understanding of DNA damage mechanisms at molecular, subcellular, cellular, organ, system and organism levels. Current strategies to investigate human health risks should be modified to increase their performance for more reliable results and also new techniques such as toxicogenomics, epigenomics and single cell approaches must be integrated into genetic safety evolutions. The explored new biomarkers by the omic techniques will provide forceful genotoxicity assessment to reduce the cancer risk.

Safinamide in the treatment of Parkinson's disease.

PubMed

Schapira, Anthony H V

2010-09-01

Current therapy for Parkinson's disease (PD) is primarily directed at reversing the motor symptoms that are the consequence of dopamine deficiency and includes levodopa, dopamine agonists and monoamine oxidase (MAO) B inhibitors. New drugs offering both dopaminergic and non-dopaminergic actions could offer a significant advantage. This review surveys the current treatment strategies for PD. Defining unmet needs and how a new compound - safinamide, which has both dopaminergic and non-dopaminergic actions - might address these. The reader will gain an understanding of safinamide and its mechanisms of action, including reversible MAOB inhibition and reduced dopamine reuptake with antiglutamatergic effects, and how it may potentially provide improvement of PD motor symptoms with an antidyskinetic effect through its effect on glutamate release. The clinical trial profile of safinamide is reviewed. Early results are promising in terms of improved motor function and reduced 'OFF' time. Additional Phase III trials are now in progress for this adjunctive indication. Finally, the reader will understand the potential role for safinamide in the selection and sequencing of drugs for PD. safinamide combines both dopaminergic and non-dopaminergic actions that may add a new dimension to PD treatment options as an adjunct to current drugs. Its efficacy is under active evaluation in Phase III clinical trials.

Repurposing Cytarabine for Treating Primary Effusion Lymphoma by Targeting Kaposi’s Sarcoma-Associated Herpesvirus Latent and Lytic Replications

PubMed Central

Gruffaz, Marion; Zhou, Shenghua; Vasan, Karthik; Rushing, Teresa; Michael, Qing Liu; Lu, Chu

2018-01-01

ABSTRACT Oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) is etiologically linked to primary effusion lymphoma (PEL), an aggressive and nontreatable malignancy commonly found in AIDS patients. In this study, we performed a high-throughput screening of 3,731 characterized compounds and identified cytarabine, approved by the FDA for treating numerous types of cancer, as a potent inhibitor of KSHV-induced PEL. We showed the high efficacy of cytarabine in the growth inhibition of various PEL cells by inducing cell cycle arrest and apoptosis. Cytarabine inhibited host DNA and RNA syntheses and therefore induced cellular cytotoxicity. Furthermore, cytarabine inhibited viral DNA and RNA syntheses and induced the rapid degradation of KSHV major latent protein LANA (latency-associated nuclear antigen), leading to the suppression of KSHV latent replication. Importantly, cytarabine effectively inhibited active KSHV replication and virion production in PEL cells. Finally, cytarabine treatments not only effectively inhibited the initiation and progression of PEL tumors but also induced regression of grown PEL tumors in a xenograft mouse model. Altogether, our study has identified cytarabine as a novel therapeutic agent for treating PEL as well as eliminating KSHV persistent infection. PMID:29739902

Diagnosis and Treatment of Transthyretin Cardiac Amyloidosis. Progress and Hope.

PubMed

González-López, Esther; López-Sainz, Ángela; Garcia-Pavia, Pablo

2017-11-01

Cardiac amyloidosis is an infiltrative disorder caused by extracellular protein deposition. Transthyretin is a proamyloidotic protein that produces one of the most frequent forms of cardiac amyloidosis, either through mutations or a wild-type form (previously known as senile amyloidosis). Until very recently, diagnosis of transthyretin amyloidosis (ATTR) was very uncommon and histological confirmation was mandatory, making diagnosis of ATTR a real challenge in daily clinical practice. Moreover, the specific therapeutic options to alter the clinical course of the disease were very limited. However, advances in cardiac imaging and diagnostic strategies have improved recognition of ATTR. In addition, several compounds able to modify the natural history of the disease are in the final phases of research, with promising results. Given that effective therapies are on the horizon, cardiologists should be well-versed in this disease and be familiar with its diagnosis and treatment. This review describes the broad clinical spectrum of ATTR in detail, as well as recent advances in the diagnosis and treatment of this condition. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Quantification of atmospheric formaldehyde by infrared absorption spectroscopy

NASA Astrophysics Data System (ADS)

Hoffnagle, John; Fleck, Derek; Rella, Chris; Kim-Hak, David

2017-04-01

Formaldehyde is a toxic, carcinogenic compound that can contaminate ambient air as a result of combustion or outgassing of commercial products such as adhesives used to fabricate plywood and to affix indoor carpeting. Like many small molecules, formaldehyde has an infrared absorption spectrum exhibiting bands of ro-vibrational transitions that are well resolved at low pressure and therefore well suited for optical analysis of formaldehyde concentration. We describe progress in applying cavity ring-down spectroscopy of the 2v5 band (the first overtone of the asymmetric C-H stretch, origin at 1770 nm) to the quantitative analysis of formaldehyde concentration in ambient air. Preliminary results suggest that a sensitivity of 1-2 ppb in a measurement interval of a few seconds, and 0.1-0.2 ppb in a few minutes, should be achievable with a compact, robust, and field-deployable instrument. Finally, we note that recent satellites monitoring snapshots of formaldehyde columns give insights into global formaldehyde production, migration and lifetime. The ability to monitor formaldehyde with a small and portable analyzer has the potential to aid in validation of these snapshots and to provide complementary data to show vertical dispersions with high spatial accuracy.

Bioinformatics and variability in drug response: a protein structural perspective

PubMed Central

Lahti, Jennifer L.; Tang, Grace W.; Capriotti, Emidio; Liu, Tianyun; Altman, Russ B.

2012-01-01

Marketed drugs frequently perform worse in clinical practice than in the clinical trials on which their approval is based. Many therapeutic compounds are ineffective for a large subpopulation of patients to whom they are prescribed; worse, a significant fraction of patients experience adverse effects more severe than anticipated. The unacceptable risk–benefit profile for many drugs mandates a paradigm shift towards personalized medicine. However, prior to adoption of patient-specific approaches, it is useful to understand the molecular details underlying variable drug response among diverse patient populations. Over the past decade, progress in structural genomics led to an explosion of available three-dimensional structures of drug target proteins while efforts in pharmacogenetics offered insights into polymorphisms correlated with differential therapeutic outcomes. Together these advances provide the opportunity to examine how altered protein structures arising from genetic differences affect protein–drug interactions and, ultimately, drug response. In this review, we first summarize structural characteristics of protein targets and common mechanisms of drug interactions. Next, we describe the impact of coding mutations on protein structures and drug response. Finally, we highlight tools for analysing protein structures and protein–drug interactions and discuss their application for understanding altered drug responses associated with protein structural variants. PMID:22552919

High-voltage positive electrode materials for lithium-ion batteries

DOE PAGES

Li, Wangda; Song, Bohang; Manthiram, Arumugam

2017-04-25

The ever-growing demand for advanced rechargeable lithium-ion batteries in portable electronics and electric vehicles has spurred intensive research efforts over the past decade. The key to sustaining the progress in Li-ion batteries lies in the quest for safe, low-cost positive electrode (cathode) materials with desirable energy and power capabilities. One approach to boost the energy and power densities of batteries is to increase the output voltage while maintaining a high capacity, fast charge–discharge rate, and long service life. Here, this review gives an account of the various emerging high-voltage positive electrode materials that have the potential to satisfy these requirementsmore » either in the short or long term, including nickel-rich layered oxides, lithium-rich layered oxides, high-voltage spinel oxides, and high-voltage polyanionic compounds. The key barriers and the corresponding strategies for the practical viability of these cathode materials are discussed along with the optimization of electrolytes and other cell components, with a particular emphasis on recent advances in the literature. Finally, a concise perspective with respect to plausible strategies for future developments in the field is also provided.« less

Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections

PubMed Central

Iversen, Patrick L.; Warren, Travis K.; Wells, Jay B.; Garza, Nicole L.; Mourich, Dan V.; Welch, Lisa S.; Panchal, Rekha G.; Bavari, Sina

2012-01-01

There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates. PMID:23202506

Improving Toxicity Assessment of Pesticide Mixtures: The Use of Polar Passive Sampling Devices Extracts in Microalgae Toxicity Tests

PubMed Central

Kim Tiam, Sandra; Fauvelle, Vincent; Morin, Soizic; Mazzella, Nicolas

2016-01-01

Complexity of contaminants exposure needs to be taking in account for an appropriate evaluation of risks related to mixtures of pesticides released in the ecosystems. Toxicity assessment of such mixtures can be made through a variety of toxicity tests reflecting different level of biological complexity. This paper reviews the recent developments of passive sampling techniques for polar compounds, especially Polar Organic Chemical Integrative Samplers (POCIS) and Chemcatcher® and the principal assessment techniques using microalgae in laboratory experiments. The progresses permitted by the coupled use of such passive samplers and ecotoxicology testing as well as their limitations are presented. Case studies combining passive sampling devices (PSD) extracts and toxicity assessment toward microorganisms at different biological scales from single organisms to communities level are presented. These case studies, respectively, aimed (i) at characterizing the “toxic potential” of waters using dose-response curves, and (ii) at performing microcosm experiments with increased environmental realism in the toxicant exposure in term of cocktail composition and concentration. Finally perspectives and limitations of such approaches for future applications in the area of environmental risk assessment are discussed. PMID:27667986

Discovery and early development of AVI-7537 and AVI-7288 for the treatment of Ebola virus and Marburg virus infections.

PubMed

Iversen, Patrick L; Warren, Travis K; Wells, Jay B; Garza, Nicole L; Mourich, Dan V; Welch, Lisa S; Panchal, Rekha G; Bavari, Sina

2012-11-06

There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates.

Inhibitory effect of turmeric curcuminoids on FLT3 expression and cell cycle arrest in the FLT3-overexpressing EoL-1 leukemic cell line.

PubMed

Tima, Singkome; Ichikawa, Hideki; Ampasavate, Chadarat; Okonogi, Siriporn; Anuchapreeda, Songyot

2014-04-25

Leukemia is a hematologic malignancy with a frequent incidence and high mortality rate. Previous studies have shown that the FLT3 gene is overexpressed in leukemic blast cells, especially in acute myeloid leukemia. In this study, a commercially available curcuminoid mixture (1), pure curcumin (2), pure demethoxycurcumin (3), and pure bisdemethoxycurcumin (4) were investigated for their inhibitory effects on cell growth, FLT3 expression, and cell cycle progression in an FLT3-overexpressing EoL-1 leukemic cell line using an MTT assay, Western blotting, and flow cytometry, respectively. The mixture (1) and compounds 2-4 demonstrated cytotoxic effects with IC50 values ranging from 6.5 to 22.5 μM. A significant decrease in FLT3 protein levels was found after curcuminoid treatment with IC20 doses, especially with mixture 1 and compound 2. In addition, mixture 1 and curcumin (2) showed activity on cell cycle arrest at the G0/G1 phase and decreased the FLT3 and STAT5A protein levels in a dose-dependent manner. Compound 2 demonstrated the greatest potential for inhibiting cell growth, cell cycle progression, and FLT3 expression in EoL-1 cells. This investigation has provided new findings regarding the effect of turmeric curcuminoids on FLT3 expression in leukemic cells.

Measuring and Perceiving Changes in Oral Complexity, Accuracy and Fluency: Examining Instructed Learners' Short-Term Gains

ERIC Educational Resources Information Center

Tonkyn, Alan Paul

2012-01-01

This paper reports a case study of the nature and extent of progress in speaking skills made by a group of upper intermediate instructed learners, and also assessors' perceptions of that progress. Initial and final interview data were analysed using several measures of Grammatical and Lexical Complexity, Language Accuracy and Fluency. These…