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Search Results: 1 - 10 of 323538 matches for " Peter J. McCarthy "
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Synthesis and In Vitro Evaluation of Novel Acyclic and Cyclic Nucleoside Analogs with a Thiadiazole Ring
Yuxiang Zhao,Peter J. McCarthy,Cyril Párkányi
ISRN Organic Chemistry , 2013, DOI: 10.1155/2013/159164
Abstract:
Synthesis and In Vitro Evaluation of Novel Acyclic and Cyclic Nucleoside Analogs with a Thiadiazole Ring
Yuxiang Zhao,Peter J. McCarthy,Cyril Párkányi
ISRN Organic Chemistry , 2013, DOI: 10.1155/2013/159164
Abstract: The synthesis of six thiadiazole nucleoside analogs is reported: 5-diacetylamino-1,2,4-thiadiazol-3-one (1), 5-amino-2- (tetrahydrofuran-2-yl)-1,2,4-thiadiazol-3-one (2), 5-amino-3-[(2′-hydroxyethoxy)methyl]-1,3,4-thiadiazol-2-one (3), 5-amino-3-(4′-hydroxy-2′-hydroxymethyl-butyl)-1,3,4-thiadiazole-2-thione (4), (R)-5-amino-3-(2′,3′-dihydroxypropyl)-1,3,4-thiadiazole-2-thione (5), and (S)-5-amino-3-(2′,3′-dihydroxypropyl)-1,3,4-thiadiazole-2-thione (6). The synthesis, characterization, and properties of these new synthesized thiadiazole derivatives are discussed. A dimerization of 5-amino-3H-1,3,4-thiadiazole-2-thione (14) by sodium nitrite resulting in di-(5-amino-1,3,4-thiadiazol-2-yl) disulfide (19) is also reported. The preliminary in vitro evaluation of these newly synthesized compounds is discussed. 1. Introduction Since Heidelberger et al. discovered 5-fluorouracil, a pyrimidine antimetabolite, in 1957, pyrimidine antimetabolites have become one of the most important groups of anticancer agents. Some pyrimidine nucleosides have been proven to possess promising anticancer activity [1–8], such as Floxuridine, Cytarabine, and Gemcitabine. Many analogs of pyrimidine nucleosides are active against viruses as well. For example, Zidovudine (Azidothymidine, AZT or ZDV), Lamivudine, Idoxuridine, Trifluridine, and Cytarabine are all used for treating viral infections [9–23]. A number of these highly successful antiviral compounds are due to the collaboration between Dracinsky et al. [17] and de Clercq and Holy [17–21] (Viread, Truvada, Atripla, Lamivudine, Vistide, Hepsera). In our laboratory, we have focused on the development of novel antimetabolites for many years, including some compounds with a thiadiazole ring. Experimental evidence indicates similarities in physical and chemical properties between a –CH=CH– bond in aromatic hydrocarbons and bivalent sulfur, –S–, in sulfur heterocycles [24, 25]. For this reason, 5-amino-2H-1,2,4-thiadiazol-3-one and 5-amino-3H-1,3,4-thiadiazol-2-one can be considered as the analogs of cytosine. Based on this analogy, within the framework of our systematic studies, we have synthesized some novel acyclic or cyclic nucleoside analogs with a thiadiazole ring instead of a pyrimidine ring. 2. Results and Discussion In the present paper, we report the preparation of 5-diacetylamino-1,2,4-thioadiazol-3-one (1)?and?five thiadiazole-based?nucleoside?analogs:?5-diacetylamino-1,2,4-thiadiazol-3-one (1), 5-amino-2?(tetrahydrofuran-2-yl)-1,2,4-thiadiazol-3-one (2),
Neglected Tropical Diseases of Oceania: Review of Their Prevalence, Distribution, and Opportunities for Control
Kevin Kline,James S. McCarthy,Mark Pearson,Alex Loukas,Peter J. Hotez
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0001755
Abstract: Among Oceania's population of 35 million people, the greatest number living in poverty currently live in Papua New Guinea (PNG), Fiji, Vanuatu, and the Solomon Islands. These impoverished populations are at high risk for selected NTDs, including Necator americanus hookworm infection, strongyloidiasis, lymphatic filariasis (LF), balantidiasis, yaws, trachoma, leprosy, and scabies, in addition to outbreaks of dengue and other arboviral infections including Japanese encephalitis virus infection. PNG stands out for having the largest number of cases and highest prevalence for most of these NTDs. However, Australia's Aboriginal population also suffers from a range of significant NTDs. Through the Pacific Programme to Eliminate Lymphatic Filariasis, enormous strides have been made in eliminating LF in Oceania through programs of mass drug administration (MDA), although LF remains widespread in PNG. There are opportunities to scale up MDA for PNG's major NTDs, which could be accomplished through an integrated package that combines albendazole, ivermectin, diethylcarbamazine, and azithromycin, in a program of national control. Australia's Aboriginal population may benefit from appropriately integrated MDA into primary health care systems. Several emerging viral NTDs remain important threats to the region.
Bacillus Strains Most Closely Related to Bacillus nealsonii Are Not Effectively Circumscribed within the Taxonomic Species Definition
K. Kealy Peak,Kathleen E. Duncan,Vicki A. Luna,Debra S. King,Peter J. McCarthy,Andrew C. Cannons
International Journal of Microbiology , 2011, DOI: 10.1155/2011/673136
Abstract: Bacillus strains with >99.7% 16S rRNA gene sequence similarity were characterized with DNA:DNA hybridization, cellular fatty acid (CFA) analysis, and testing of 100 phenotypic traits. When paired with the most closely related type strain, percent DNA:DNA similarities (% ) for six Bacillus strains were all far below the recommended 70% threshold value for species circumscription with Bacillus nealsonii. An apparent genomic group of four Bacillus strain pairings with 94%–70% was contradicted by the failure of the strains to cluster in CFA- and phenotype-based dendrograms as well as by their differentiation with 9–13 species level discriminators such as nitrate reduction, temperature range, and acid production from carbohydrates. The novel Bacillus strains were monophyletic and very closely related based on 16S rRNA gene sequence. Coherent genomic groups were not however supported by similarly organized phenotypic clusters. Therefore, the strains were not effectively circumscribed within the taxonomic species definition.
Bacillus Strains Most Closely Related to Bacillus nealsonii Are Not Effectively Circumscribed within the Taxonomic Species Definition
K. Kealy Peak,Kathleen E. Duncan,Vicki A. Luna,Debra S. King,Peter J. McCarthy,Andrew C. Cannons
International Journal of Microbiology , 2011, DOI: 10.1155/2011/673136
Abstract: Bacillus strains with >99.7% 16S rRNA gene sequence similarity were characterized with DNA:DNA hybridization, cellular fatty acid (CFA) analysis, and testing of 100 phenotypic traits. When paired with the most closely related type strain, percent DNA:DNA similarities (% ) for six Bacillus strains were all far below the recommended 70% threshold value for species circumscription with Bacillus nealsonii. An apparent genomic group of four Bacillus strain pairings with 94%–70% was contradicted by the failure of the strains to cluster in CFA- and phenotype-based dendrograms as well as by their differentiation with 9–13 species level discriminators such as nitrate reduction, temperature range, and acid production from carbohydrates. The novel Bacillus strains were monophyletic and very closely related based on 16S rRNA gene sequence. Coherent genomic groups were not however supported by similarly organized phenotypic clusters. Therefore, the strains were not effectively circumscribed within the taxonomic species definition. 1. Introduction CBD 118 was one of the two first Bacillus strains not related to the B. cereus group reported to harbor the capsule genes carried on pXO2 by Bacillus anthracis (USF Center for Biological Defense (CBD)) [1, 2]. Luna et al. isolated and sequenced the capsule operon (capA, capB, capC, capD, and promoter), repA, capR, acpA, IS1627, ORF43, ORF48, and ORF61 on a large plasmid in CBD 118 [1]. Its status as a carrier of B. anthracis capsule genes spurred research into determining its closest relatives, to aid in circumscribing the reservoir of genes essential for virulence in B. anthracis. When near full length 16S rRNA gene sequences were compared, the most similar type strains to strain CBD 118 were Bacillus circulans ATCC (98.9%) and Bacillus nealsonii DSM (99.3%). Strain CBD 118 differed from B. circulans ATCC and B. nealsonii DSM for 10 and 12 of 100 phenotypic traits evaluated, respectively. The percentages of DNA:DNA binding in two pairings each of strain CBD 118 to B. circulans ATCC and B. nealsonii DSM were 12.5 and 10.2% and 10.8 and 8.3%, respectively. Thus, strain CBD 118 is differentiated by phenotypic and genome-based methods from the only validly named species with greater than 98.7% 16S rRNA gene sequence similarity [3–5]. Strain CBD 118 was the sole exemplar of a novel species. Prior to the proposal of novel species, studies of ten or more strains are recommended in order to detail intraspecies diversity and to foster appropriate type strain assignment [6–8]. To identify the requisite closely related strains, the
Prostaglandin E2 Induction during Mouse Adenovirus Type 1 Respiratory Infection Regulates Inflammatory Mediator Generation but Does Not Affect Viral Pathogenesis
Mary K. McCarthy, Rachael E. Levine, Megan C. Procario, Peter J. McDonnell, Lingqiao Zhu, Peter Mancuso, Leslie J. Crofford, David M. Aronoff, Jason B. Weinberg
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077628
Abstract: Respiratory viruses cause substantial disease and are a significant healthcare burden. Virus-induced inflammation can be detrimental to the host, causing symptoms during acute infection and leading to damage that contributes to long-term residual lung disease. Prostaglandin E2 (PGE2) is a lipid mediator that is increased in response to many viral infections, and inhibition of PGE2 production during respiratory viral infection often leads to a decreased inflammatory response. We tested the hypothesis that PGE2 promotes inflammatory responses to mouse adenovirus type 1 (MAV-1) respiratory infection. Acute MAV-1 infection increased COX-2 expression and PGE2 production in wild type mice. Deficiency of the E prostanoid 2 receptor had no apparent effect on MAV-1 pathogenesis. Virus-induced induction of PGE2, IFN-γ, CXCL1, and CCL5 was reduced in mice deficient in microsomal PGE synthase-1 (mPGES-1-/- mice). However, there were no differences between mPGES-1+/+ and mPGES-1-/- mice in viral replication, recruitment of leukocytes to airways or lung inflammation. Infection of both mPGES?1+/+ and mPGES-1-/- mice led to protection against reinfection. Thus, while PGE2 promotes the expression of a variety of cytokines in response to acute MAV-1 infection, PGE2 synthesis does not appear to be essential for generating pulmonary immunity.
High star formation rates as the origin of turbulence in early and modern disk galaxies
Andrew W. Green,Karl Glazebrook,Peter J. McGregor,Roberto G. Abraham,Gregory B. Poole,Ivana Damjanov,Patrick J. McCarthy,Matthew Colless,Robert G. Sharp
Physics , 2010, DOI: 10.1038/nature09452
Abstract: High spatial and spectral resolution observations of star formation and kinematics in early galaxies have shown that two-thirds are massive rotating disk galaxies with the remainder being less massive non-rotating objects. The line of sight averaged velocity dispersions are typically five times higher than in today's disk galaxies. This has suggested that gravitationally-unstable, gas-rich disks in the early Universe are fuelled by cold, dense accreting gas flowing along cosmic filaments and penetrating hot galactic gas halos. However these accreting flows have not been observed, and cosmic accretion cannot power the observed level of turbulence. Here we report on a new sample of rare high-velocity-dispersion disk galaxies we have discovered in the nearby Universe where cold accretion is unlikely to drive their high star-formation rates. We find that the velocity dispersion is most fundamentally correlated with their star-formation rates, and not their mass nor gas fraction, which leads to a new picture where star formation itself is the energetic driver of galaxy disk turbulence at all cosmic epochs.
Fusing the coordinates of quantum superspace
Peter Bouwknegt,Jim McCarthy,Peter van Nieuwenhuizen
Physics , 1996, DOI: 10.1016/S0370-2693(96)01679-6
Abstract: We introduce the notion of a fused quantum superplane by allowing for terms $\theta\theta\sim x$ in the defining relations. We develop the differential calculus for a large class of fused quantum superplanes related to particular solutions of the Yang-Baxter equation.
microRNA and skeletal muscle function: novel potential roles in exercise, diseases, and aging
John J. McCarthy
Frontiers in Physiology , 2014, DOI: 10.3389/fphys.2014.00290
Abstract:
Shock-Free Wave Propagation in Gauge Theories
J. McCarthy,O. Sarioglu
Physics , 1999, DOI: 10.1023/A:1003659520136
Abstract: We present the shock-free wave propagation requirements for massless fields. First, we briefly argue how the "completely exceptional" approach, originally developed to study the characteristics of hyperbolic systems in 1+1 dimensions, can be generalized to higher dimensions and used to describe propagation without emerging shocks, with characteristic flow remaining parallel along the waves. We then study the resulting requirements for scalar, vector, vector-scalar and gravity models and characterize physically acceptable actions in each case.
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