A pyrimidine nucleoside formed in the body by the deamination of CYTARABINE.

Suicide prodrugs activated by thymidylate synthase: rationale for treatment and noninvasive imaging of tumors with deoxyuridine analogues. (1/171)

Most tumors are resistant to therapy by thymidylate synthase (TS) inhibitors due to their high levels of TS. Instead of inhibiting TS, we hypothesized that it was possible to use this enzyme to activate suicide prodrugs (deoxyuridine analogues) to more toxic species (thymidine analogues). Tumors with high levels of TS could be particularly sensitive to deoxyuridine analogues because they would be more efficient in producing the toxic methylated species. Furthermore, the accumulation of methylated species within tumors could be visualized externally if a tracer dose of the deoxyuridine analogue was tagged with an isotope, preferably a positron emitter, such as 18F. Higher accumulation of isotope indicates higher activity of TS and lower sensitivity of the tumor to TS inhibitors, but perhaps more sensitivity to therapy with deoxyuridine analogues as suicide prodrugs. 2'-F-ara-deoxyuridine (FAU) was used as a prototype to demonstrate these concepts experimentally. FAU readily entered cells and was phosphorylated, methylated, and subsequently incorporated into cellular DNA. Among different cell lines, FAU produced varying degrees of growth inhibition. Greater DNA incorporation (e.g., for CEM and U-937 cells) was reflected as increased toxicity. FAU produced less DNA incorporation in Raji or L1210 cells, and growth rate was minimally decreased. As the first demonstration that cells with high levels of TS activity can be more vulnerable to therapy than cells with low TS activity, this preliminary work suggests a new therapeutic approach for common human tumors that were previously resistant. Furthermore, it appears that the TS activity of tumors could be noninvasively imaged in situ by tracer doses of [18F]FAU and that this phenotypic information could guide patient therapy.  (+info)

Imaging adenoviral-mediated herpes virus thymidine kinase gene transfer and expression in vivo. (2/171)

The feasibility of noninvasive imaging of adenoviral-mediated herpes virus type one thymidine kinase (HSV1-tk) gene transfer and expression was assessed in a well-studied animal model of metastatic colon carcinoma of the liver. Tumors were produced in syngeneic BALB/c mice by intrahepatic injection of colon carcinoma cells (MCA-26). Seven days later, three different doses (3 x 10(8), 1 x 10(8), and 3 x 10(7) plaque-forming units (pfu) of the recombinant adenoviral vector ADV. Rous sarcoma virus (RSV)-tk bearing the HSV1-tk gene were administered by intratumoral injection in separate groups of mice. Two control groups of tumor-bearing mice received intratumoral injections of the control adenoviral vector dl-312 or buffer alone, respectively. T2-weighted magnetic resonance (MR) images of mice were obtained before administering the virus and provided an anatomical reference of hepatic tumor localization. Eighteen h after the virus injection, one group of animals was given i.v. injections of 300 microCi of no-carrier-added 5-[131I]-2'-fluoro-1-beta-D-arabinofuranosyluracil (FIAU) and imaged 24 h later with a gamma camera. In some animals, the tumors were sampled and processed for histology and quantitative autoradiography (QAR). The gamma camera images demonstrated highly specific localization of [131I]FIAU-derived radioactivity to the area of ADV.RSV-tk-injected tumors in the liver, which was confirmed by coregistering the gamma camera and T2-weighted MR images. There was no accumulation of [131I]FIAU-derived radioactivity in tumors that were injected with the control vector or injection solution alone. A more precise distribution of radioactivity in the area of transfected tumor was obtained by histological and QAR comparisons. A heterogeneous pattern of radioactivity distribution in transfected tumors was observed. A punctate pattern of radioactivity distribution was observed in peritumoral liver tissue in animals given injections of 3 x 10(8) and 1 x 10(8) pfu of ADV.RSV-tk but not in animals given injections of 3 x 10(7) pfu nor in control animals. A QAR-microscopic comparison showed that the punctate areas of radioactivity colocalized with cholangial ducts. The level of [131I]FIAU-derived radioactivity accumulation (HSV1-tk expression) in the transfected tumors was viral dose-dependent. The viral dose-dependency of radioactivity accumulation was more pronounced in peritumoral liver, which was confirmed by reverse transcription-PCR analysis. A separate group of tumor-bearing animals received different doses of ADV.RSV-tk vector followed by treatment with ganciclovir (GCV), 10 mg/kg i.p. b.i.d. for 6 days. The ADV.RSV-tk transfected tumors significantly regressed with GCV treatment; the control tumors continued to grow. During the GCV treatment, the levels of liver transaminases (ALT and AST) were significantly increased in animals that received injections of 3 x 10(8) and 1 x 10(8) pfu of ADV.RSV-tk but not in animals that received injections of 3 x 10(7) pfu and in control animals. The observed liver toxicity confirms the results of gamma camera and QAR imaging, which demonstrated an unwanted spread of ADV.RSV-tk vector and HSV1-tk expression in peritumoral and remote liver tissue at higher doses. These and our previous results indicate that noninvasive imaging of adenoviral-mediated HSV1-tk gene expression is feasible for monitoring cancer gene therapy in patients.  (+info)

Brca1 controls homology-directed DNA repair. (3/171)

Germline mutations in BRCA1 confer a high risk of breast and ovarian tumors. The role of BRCA1 in tumor suppression is not yet understood, but both transcription and repair functions have been ascribed. Evidence that BRCA1 is involved in DNA repair stems from its association with RAD51, a homolog of the yeast protein involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination. We report here that Brca1-deficient mouse embryonic stem cells have impaired repair of chromosomal DSBs by homologous recombination. The relative frequencies of homologous and nonhomologous DNA integration and DSB repair were also altered. The results demonstrate a caretaker role for BRCA1 in preserving genomic integrity by promoting homologous recombination and limiting mutagenic nonhomologous repair processes.  (+info)

Comparative in vitro and in vivo cytotoxic activity of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and its arabinosyl derivative, (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU), against tumor cells expressing either the Varicella zoster or the Herpes simplex virus thymidine kinase. (4/171)

The inhibitory effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and its arabinosyl derivative (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU) on the growth of both MDA-MB-435 human breast carcinoma and 9L rat gliosarcoma cells expressing the thymidine kinase (tk)-encoding gene of the Varicella zoster virus (VZV) or the Herpes simplex virus (HSV) were evaluated. In vitro, BVDU and BVaraU effectively killed both cell types expressing VZVtk, with 50% inhibitory concentration values ranging from 0.06 to 0.4 microM, whereas ganciclovir (GCV) lacked activity. On HSVtk+ cells, BVDU had high cytotoxic activity, with 50% inhibitory concentration values that were similar to those of GCV, whereas BVaraU was inactive. In vivo, BVDU applied intraperitoneally caused a 50% tumor growth inhibition in nude mice inoculated subcutaneously with VZVtk+ as well as HSVtk+ mammary tumor cells. In mice and at variance with the in vitro results, BVaraU had very little activity against the VZVtk+ mammary cells; GCV had the highest activity on the HSVtk+ cells, resulting in a 50% eradication of the tumors. With the 9L rat gliosarcoma model, the VZVtk/BVDU system completely failed to inhibit the development of VZVtk+ glioma tumors induced subcutaneously in syngeneic rats, although BVDU had a similar 45-minute half-life in both rats and mice. Factors other than degradation of the prodrug and related to the mode of action of these analogs are possibly involved in the observed discrepancies between the in vitro and in vivo results.  (+info)

Functional coexpression of HSV-1 thymidine kinase and green fluorescent protein: implications for noninvasive imaging of transgene expression. (5/171)

Current gene therapy technology is limited by the paucity of methodology for determining the location and magnitude of therapeutic transgene expression in vivo. We describe and validate a paradigm for monitoring therapeutic transgene expression by noninvasive imaging of the herpes simplex virus type 1 thymidine kinase (HSV-1-tk) marker gene expression. To test proportional coexpression of therapeutic and marker genes, a model fusion gene comprising green fluorescent protein (gfp) and HSV-1-tk genes was generated (tkgfp gene) and assessed for the functional coexpression of the gene product, TKGFP fusion protein, in rat 9L gliosarcoma, RG2 glioma, and W256 carcinoma cells. Analysis of the TKGFP protein demonstrated that it can serve as a therapeutic gene by rendering tkgfp transduced cells sensitive to ganciclovir or as a screening marker useful for identifying transduced cells by fluorescence microscopy or fluorescence-activated cell sorting (FACS). TK and GFP activities in the TKGFP fusion protein were similar to corresponding wild-type proteins and accumulation of the HSV-1-tk-specific radiolabeled substrate, 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyl-5-iodo-uracil (FIAU), in stability transduced clones correlated with gfp-fluorescence intensity over a wide range of expression levels. The tkgfp fusion gene itself may be useful in developing novel cancer gene therapy approaches. Valuable information about the efficiency of gene transfer and expression could be obtained by non-invasive imaging of tkgfp expression with FIAU and clinical imaging devices (gamma camera, positron-emission tomography [PET], single photon emission computed tomography [SPECT]), and/or direct visualization of gfp expression in situ by fluorescence microscopy or endoscopy.  (+info)

Uptake of radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil in cardiac cells after adenoviral transfer of the herpesvirus thymidine kinase gene: the cellular basis for cardiac gene imaging. (6/171)

BACKGROUND: Gene therapy is a promising approach for the treatment of cardiac diseases. Coexpression of therapeutic genes with a suitable marker gene would allow for the noninvasive imaging of successful gene transfer and expression via radiolabeled marker substrates. In the present study, such an approach was first applied to cardiac tissue. METHODS AND RESULTS: The combination of the herpesvirus thymidine kinase reporter gene (HSV1-tk) and radiolabeled 2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil (FIAU) was evaluated. H9c2 rat cardiomyoblasts were infected in vitro with a replication-defective HSV1-tk-containing adenovirus and a negative control virus. The intracellular uptake of [(14)C]FIAU increased with increasing multiplicity of infection and with time after infection. Uptake in negative controls remained <15% of positive controls. Additionally, vectors were applied intramyocardially in Wistar rats. The marker substrate [(125)I]FIAU was injected intravenously 3 days later, and animals were killed after 24 hours. Autoradiographically, regional transgene expression was clearly identified in animals receiving the adenovirus containing HSV1-tk (3. 4+/-2.2-fold increase of radioactivity at vector administration site compared with remote myocardium), whereas nonspecific uptake in negative controls was low (<10% of positive controls). CONCLUSIONS: Using an adenoviral vector, HSV1-tk can be successfully expressed in cardiac cells in vitro and in vivo, yielding high uptake of radiolabeled FIAU. The results suggest that imaging transgene expression in the heart is feasible and may be used to monitor gene therapy noninvasively.  (+info)

A transgenic mouse model for inducible and reversible dysmyelination. (7/171)

Oligodendrocytes are glial cells devoted to the production of myelin sheaths. Myelination of the CNS occurs essentially after birth. To delineate both the times of oligodendrocyte proliferation and myelination, as well as to study the consequence of dysmyelination in vivo, a model of inducible dysmyelination was developed. To achieve oligodendrocyte ablation, transgenic animals were generated that express the herpes virus 1 thymidine kinase (HSV1-TK) gene under the control of the myelin basic protein (MBP) gene promoter. The expression of the MBP-TK transgene in oligodendrocytes is not toxic on its own; however, toxicity can be selectively induced by the systemic injection of animals with nucleoside analogs, such as FIAU [1-(2-deoxy-2-fluoro-beta-delta-arabinofuranosyl)-5-iodouracil]. This system allows us to control the precise duration of the toxic insult and the degree of ablation of oligodendrocytes in vivo. We show that chronic treatment of MBP-TK mice with FIAU during the first 3 postnatal weeks triggers almost a total depletion of oligodendrocytes in the CNS. These effects are accompanied by a behavioral phenotype characterized by tremors, seizures, retarded growth, and premature animal death. We identify the period of highest oligodendrocytes division in the first 9 postnatal days. Delaying the beginning of FIAU treatments results in different degrees of dysmyelination. Dysmyelination in MBP-TK mice is always accompanied by astrocytosis. Thus, this transgenic line provides a model to study the events occurring during dysmyelination of various intensities. It also represents an invaluable tool to investigate remyelination in vivo.  (+info)

Kinetics of hepadnavirus loss from the liver during inhibition of viral DNA synthesis. (8/171)

Hepadnaviruses replicate by reverse transcription, which takes place in the cytoplasm of the infected hepatocyte. Viral RNAs, including the pregenome, are transcribed from a covalently closed circular (ccc) viral DNA that is found in the nucleus. Inhibitors of the viral reverse transcriptase can block new DNA synthesis but have no direct effect on the up to 50 or more copies of cccDNA that maintain the infected state. Thus, during antiviral therapy, the rates of loss of cccDNA, infected hepatocytes (1 or more molecules of cccDNA), and replicating DNAs may be quite different. In the present study, we asked how these losses compared when woodchucks chronically infected with woodchuck hepatitis virus were treated with L-FMAU [1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl) uracil], an inhibitor of viral DNA synthesis. Viremia was suppressed for at least 8 months, after which drug-resistant virus began replicating to high titers. In addition, replicating viral DNAs were virtually absent from the liver after 6 weeks of treatment. In contrast, cccDNA declined more slowly, consistent with a half-life of approximately 33 to 50 days. The loss of cccDNA was comparable to that expected from the estimated death rate of hepatocytes in these woodchucks, suggesting that death of infected cells was one of the major routes for elimination of cccDNA. However, the decline in the actual number of infected hepatocytes lagged behind the decline in cccDNA, so that the average cccDNA copy number in infected cells dropped during the early phase of therapy. This observation was consistent with the possibility that some fraction of cccDNA was distributed to daughter cells in those infected hepatocytes that passed through mitosis.  (+info)

Fialuridine, or 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU), is a nucleoside analogue that was investigated as a potential therapy for hepatitis B virus infection. In a 1993 clinical study at the NIH, unexpected toxicity led to the death of 5 out of 15 patients from liver failure associated with lactic acidosis; two further participants required liver transplantation. This toxicity was unusual in that it was not predicted by animal studies. It is suspected that the drugs toxicity was due to its damaging mitochondria. Tujios S, Fontana RJ. Mechanisms of drug-induced liver injury: from bedside to bench. Nat Rev Gastroenterol Hepatol. 2011 Apr;8(4):202-11. Review. PMID 21386809 McKenzie R, Fried MW, Sallie R, et al. (1995). Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. N. Engl. J. Med. 333 (17): 1099-1105. doi:10.1056/NEJM199510263331702. PMID 7565947. Thomson, Larry (1 March 1994). The Cure that ...
FOSTER CITY, Calif., Jun 24, 2003 (BUSINESS WIRE) -- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the company is ending its licensing agreement with Bukwang Pharm. Ind. Co., Ltd for the development and commercialization of clevudine. Formerly known as L-FMAU, clevudine is an investigational pyrimidine nucleoside analogue currently in Phase I/II development for the treatment of chronic hepatitis B. The termination will be effective August 6, 2003. In February 1998, Triangle Pharmaceuticals entered into a licensing agreement with Bukwang for worldwide rights to clevudine in all markets except Korea. In January 2003, Gilead acquired Triangle Pharmaceuticals. Under the terms of the licensing agreement, Gilead does not owe any further payments to Bukwang. Gilead will meet its ongoing obligations under the agreement until such time that they can be transferred to Bukwang or a new partner. We have valued our partnership with Bukwang, and while clevudine is an interesting compound, we have ...
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A synthetic pyrimidine analogue with activity against hepatitis B virus (HBV). Intracellularly, clevudine is phosphorylated to its active metabolites, clevudine monophosphate and triphosphate. The triphosphate metabolite competes with thymidine for incorporation into viral DNA, thereby causing DNA chain termination and inhibiting the function of HBV DNA polymerase (reverse transcriptase). Clevudine has a long half-life and shows significant reduction of covalently closed circular DNA (cccDNA), therefore the patient is less likely to have a relapse after treatment is discontinued.
Subjects will be dosed with [124I]FIAU at Time 0 on Day 0, and a PET-CT scan will be conducted immediately after the injection. Imaging will be repeated at 2 hours, 4 hours, 6 hours, 24 hours, 48 hours, and 72 hours after dosing.. All images generated will be reviewed for biodistribution and dosimetry. ...
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The objectives of this study are to compare in nucleoside treatment-naïve subjects, the efficacy and safety of clevudine 30 mg once daily versus adefovir 10 mg once daily, each as monotherapy, for 48 weeks, 72 weeks, and 96 weeks.. ...
The 42nd Annual Meeting of the European Association for the Study of the Liver Pharmasset announced today that presentations of preclinical studies of Clevudine
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5-Iodocytosine; 5-Iodocytosine is a modified pyrimidine used to synthesize other molecules such as pyrrolocytosine and biologically active derivatives.
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Chemical Names: 2-Fluoro-2-deoxyadenosine; 2-F-dA Catalog Number: 01-0600 CAS Number: 64183-27-3 Molecular Formula: C10H12FN5O5 Molecular Weight: 269.2
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The first enantioselective total synthesis of (+)-stachyflin, a potential anti-influenza A virus agent, was achieved; the method features a BF3·Et2O-induced domino epoxide-opening/rearrangement/cyclization reaction to stereoselectively form the requisite pentacyclic ring system in one step.
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16S rRNA (uracil1498-N3)-methyltransferaseS-adenosyl-L-methionine + uracil1498 in 16S rRNA = S-adenosyl-L-homocysteine + N3-methyluracil1498 in 16S rRNA ...
A variety of different methods for the evaluation of antiviral agents in cell culture systems are briefly reviewed. It has been repeatedly noted that many test conditions such as the cell culture system, virus strain, virus challenge dose, virus input multiplicity of infection, and time of harvesting, etc., can substantially affect or even alter the test results, thus making comparative studies and unambiguous evaluations very difficult. Attempts are made to discuss previous test methods together with our recent studies with the aim to simplify test procedures and assay methods. Suggestions are proposed for in vitro evaluation of new antiviral agents. It is hoped that this review will alarm investigators to the problems of assaying new antiviral agents. If the suggestions made in this review can be followed, the screening of the enormous number of promising antiviral compounds may be made more efficiently in the near future.
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TY - JOUR. T1 - Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B. AU - Byung, Chul Yoo. AU - Ju, Hyun Kim. AU - Chung, Young Hwa. AU - Kwan, Sik Lee. AU - Seung, Woon Paik. AU - Soo, Hyung Ryu. AU - Byung, Hoon Han. AU - Han, Joon Yeol. AU - Kwan, Soo Byun. AU - Cho, Mong. AU - Lee, Heon Ju. AU - Kim, Tae Hun. AU - Cho, Se Hyun. AU - Park, Joong Won. AU - Um, Soon Ho. AU - Seong, Gyu Hwang. AU - Young, Soo Kim. AU - Lee, Youn Jae. AU - Chae, Yoon Chon. AU - Kim, Byung Ik. AU - Lee, Young Suk. AU - Yang, Jin Mo. AU - Haak, Cheoul Kim. AU - Jae, Seok Hwang. AU - Choi, Sung Kyu. AU - Kweon, Young Oh. AU - Jeong, Sook Hyang. AU - Lee, Myung Seok. AU - Choi, Jong Young. AU - Kim, Dae Ghon. AU - Yun, Soo Kim. AU - Heon, Young Lee. AU - Yoo, Kwon. AU - Yoo, Hee Won. AU - Lee, Hyo Suk. PY - 2007/5. Y1 - 2007/5. N2 - Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study ...
Renal useful decline that is frequently seen during chronic hepatitis B (CHB) treatment can exert adverse effects about overall prognosis. renal practical decrease. A total of 4178 individuals were adopted up for a median 23 weeks. Antiviral providers included lamivudine (17.0%), adefovir (3.7%), entecavir (70.4%), telbivudine (0.6%), tenofovir (4.0%), or clevudine (4.3%). Renal practical decrease occurred in 706 (16.9%) individuals. Based on multivariate Cox regression analysis, age, hypertension, diabetes, history of liver or kidney transplantation, underlying underlying CKD, and simultaneous administration of diuretics improved the hazard percentage for renal practical decrease; however, clevudine reduced risk. The eGFR significantly improved over time in individuals receiving telbivudine or clevudine compared with lamivudine. Among the 3175 individuals adopted up for more than 1 year, 407 (12.8%) individuals experienced quick CKD progression. Individuals with quick CKD progression showed ...
Article Assessment of burden of virus agents in an urban sewage treatment plant in Rio de Janeiro, Brazil. Sewage discharge is considered to be the main source of virus contamination in aquatic environments. There is no correlation between the presen...
X-irradiated 5-nitrobarbituric acid, 5-nitroorotic acid, and 5-nitro-4,6-dihydroxy-pyrimidine show distinctive ESR spectra with very anisotropic nitrogen coupling, essentially the same as 5-nitrouracil. The 5-nitrouracil radical has been identified as an iminoxyl radical formed by a mechanism which abstracts an oxygen from the nitro group leaving the unpaired electron coupling to the nitrogen of the nitro group. It is clear that these other nitropyrimidines yield similar iminoxyl radicals. The only reported nitropyrimidine which yields different radical structures is 5-nitro-6-methyluracil which has been investigated at 77°K and 300°K by other workers. On the basis of this experimental data, INDO molecular orbital calculations, and the proposed mechanism of formation of the 5-nitro uracil radical which fits also the other nitropyrimidines, we can now propose radical structures for the low temperature and room temperature 5-nitro-6-methyluracil radicals. Our proposed 77°K radical is formed by ...
BACKGROUND: Alzheimers disease (AD) is the major age-related progressive neurodegenerative disorder. The brain of AD patients suffers from loss of cholinergic neurons and decreased number of synapses [1]. AD is caused by an imbalance between Aβ production and clearance, resulting in increased amount of Aβ in various forms [2]. Reduction of Aβ production and increasing clearance of Aβ pathogenic forms are key targets in the development of potential therapeutic agents for AD treatment. Unfortunately, only nosotropic approaches for treatment of AD are currently effective in humans. These approaches mainly focus on the inhibition of brain acetyl-cholinesterase (AChE) to increase lifetime of cerebral acetylcholine [3]. It is important to emphasize that AChE itself promotes the formation of Aβ fibrils in vitro and Aβ plaques in the cerebral cortex of transgenic mouse models of AD [4]. This property of AChE results from interaction between Aβ and the peripheral anionic site of the enzyme (PAS) ...
TABLE-US-00001 TABLE 1 Activity of Pt supported on zeolites and metal-exchanged zeolites as a function of composition, structure, and preparative method. Aging NH3 NH3 N2 Zeolite washct Temp/ conv. N2 conv. sel. structure Pt Pt Cu loading time/ %, sele. % %, %, Ex. typea SARb method ppmc %d g/in3 H2Oe 250° C. 250° C. 400° C. 400° C. 1A FAU 5.2 EXf 1925 2.02 1.493 fresh 98 73 98 69 1B FAU 5.2 EX 1925 2.02 1.493 750/25/10 98 71 98 48 1C FAU 5.2 EX 1925 2.02 1.479 750/25/0 94 74 98 62 1D FAU 5.2 EX 2239 0 1.441 750/5/10 94 57 98 23 1E FAU 5.2 EX 2107 1.12 1.525 750/5/10 95 62 99 40 1F FAU 5.2 EX 1916 2.12 1.424 750/5/10 93 78 97 53 1G FAU 5.2 EX 2003 3.19 1.483 750/5/10 94 81 98 50 1H FAU 5.2 EX 2107 1.12 1.525 fresh 95 60 98 53 1I FAU 5.2 EX 2328 1.19 1.398 fresh 0 -- 19 95 1J FAU 30 EX 1799 0.54 1.61 fresh 58 80 98 46 1K FAU 30 EX 1799 0.54 1.61 750/5/10 7 91 97 58 1L BEA 30 IMg 2000 -- 1.487 fresh 64 66 98 42 1M BEA 30 IM 2000 -- 1.449 750/25/10 7 74 96 48 1N BEA 30 EX 2340 -- 1.695 fresh 93 ...
Nucleic acid components and their analogues. CXLVI. Preparation of some nucleotide derivatives of 6-methyluridine, 3-(β-D-ribofuranosyl)uracil, and 3-(β-D-ribofuranosyl)-6-methyluracil. Investigations of their template activity and behaviour towards some nucleolytic enzymes ...
When infectious disease pandemics emerge, viruses tend to be the most lethal. Experts are working on ways to find new antiviral drug treatments, as well as to prevent epidemics from emerging in the first place.
The Freie Arbeiter_innen Union Bern is financed exclusively by membership fees and donations. In order to maintain its independence, it rejects state subsidies or company contributions.. Do you also want to support the work of the Freie Workers Union Bern? Then transfer a donation to the following postal account. Of course you can also set up a standing order.. FAU Bern. Postfach 2368. 3001 Bern. Post account: 30-276725-1. IBAN: CH25 0900 0000 3027 6725 1 For Members: Please also note your Member Number for your Member Fees!. ...
Please note: The research portal is in the set-up period and includes only information that was permitted for public display. Ok, got it ...
Please note: The research portal is in the set-up period and includes only information that was permitted for public display. Ok, got it ...
-Lauren Mercado, of Boca Raton, writes a message on a square piece of cloth that will be part of an education and prevention AIDS quilt . Duing World AIDS day at FAU in Boca Raton. Florida Atlantic Universityís Student Health Services and the LGBTQA Resource Center hosted the event which provided...
Prof. Dr.-Ing. Marc Stamminger. Prof. Dr. Michael Schmiedeberg. Prof. Dr. Stefan Funk. Prof. Dr. Lutz Schröder. Prof. Dr. Wolfgang Stummer. ...
The structure was refined using the REFMAC program. The R value is 0.19806 for 42600 reflections in the resolution range 48.88 to 2.87 Ångstroms with Fobs , 0.0 sigma(Fobs) and with I , 0.0 sigma(I) ...
US EPA PC Code ); 012303 (US EPA PC Code Text ); 5-Bromo-3-sec-butyl-6-methyluracil, sodium salt; 5-Bromo-6-methyl-3-(1-methylpropyl)-2,4(1H,3H)-pyrimidinedione, sodium salt; 69484-12-4 (CAS number); 69484124; 69484124 (CAS number without hyphens); 842 (CA DPR Chem Code) ); Bromacil, sodium salt; BROMACIL, SODIUM SALT (CA DPR Chem Code Text ); Bromacilsodiumsalt; Uracil, 5-bromo-3-sec-butyl-6-methyl-, sodium ...
FAU - FAU (untagged)-Human Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV) ubiquitously expressed (FAU) available for purchase from OriGene - Your Gene Company.
Cytarabine is rapidly metabolized and is not effective orally; less than 20 percent of the orally administered dose is absorbed from the gastrointestinal tract.. Following rapid intravenous injection of cytarabine labeled with tritium, the disappearance from plasma is biphasic. There is an initial distributive phase with a half-life of about 10 minutes, followed by a second elimination phase with a half-life of about 1 to 3 hours. After the distributive phase, more than 80 percent of plasma radioactivity can be accounted for by the inactive metabolite 1-β-D-arabinofuranosyluracil (ara-U). Within 24 hours about 80 percent of the administered radioactivity can be recovered in the urine, approximately 90 percent of which is excreted as ara-U.. Relatively constant plasma levels can be achieved by continuous intravenous infusion.. After subcutaneous or intramuscular administration of cytarabine labeled with tritium, peak-plasma levels of radioactivity are achieved about 20 to 60 minutes after ...
Antiviral Use of the Amino Acid NAC, N-acetyl-L-cysteine: VIDEO review 1 hour 42 minutes (2019): Personal note from Dr Vasquez: I had studied nutrition for at least 25 years and had written my first antiviral nutrition protocol in 2009 and the developed form of that work in 2014 as Antiviral Nutrition; as such, I did not expect to find so much rich information when I began to review the data on the amino acid NAC, the acetylated form of L-cysteine. In truth, I was amazed at the strength and depth of the research on this topic, and I was likewise dumbfounded that this powerful train of therapy was derailed almost as soon as it had been initially validated, at a time that coinsided with the introduction of a multibillion-dollar market for new antiviral drugs. I also realized that we had not simply underused NAC but that we had grossly underestimated the proper dosage by at least 75%. In this video, I review an abundance of research, ultimately proving that NAC has a wide range of uses within the ...
Optical imaging of whole, living animals has proven to be a powerful tool in multiple areas of preclinical research and has allowed noninvasive monitoring of immune responses, tumor and pathogen growth, and treatment responses in longitudinal studies. However, fluorescence-based studies in animals are challenging because tissue absorbs and autofluoresces strongly in the visible light spectrum. These optical properties drive development and use of fluorescent labels that absorb and emit at longer wavelengths. Here, we present a far-red absorbing fluoromodule-based reporter/probe system and show that this system can be used for imaging in living mice. The probe we developed is a fluorogenic dye called SC1 that is dark in solution but highly fluorescent when bound to its cognate reporter, Mars1. The reporter/probe complex, or fluoromodule, produced peak emission near 730 nm. Mars1 was able to bind a variety of structurally similar probes that differ in color and membrane permeability. We ...
Ah, Game Week II is in full gear. Players will be back at practice this afternoon, and South Carolina (home of Joe ?You Lie? Wilson) on the not-so-distant horizon.FAU is thin on its defensive line,
For example, we can ask a question in 10 different ways with 10 different intents, and the FAU of Ken Kesey will respond differently to each one based on the nature of our intent and the way we ask the question. But left to itself, the FAU of Ken Kesey cannot innovate on its own because the real Ken Kesey has moved on and the FAU is now a closed system. However, innovation and free will awareness canbleed into the responses we get if higher aspects of the FAU get involved ...
PMID- 29303721 OWN - NLM STAT- MEDLINE DCOM- 20180110 LR - 20180110 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 390 IP - 10114 DP - 2018 Dec 23 TI - Concerns about cardiotoxicity in the HERA trial. PG - 2767 LID - S0140-6736(17)31954-2 [pii] LID - 10.1016/S0140-6736(17)31954-2 [doi] FAU - Levy, Antonin AU - Levy A AD - Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif 94800, France; Faculte de Medecine, Universite Paris-Saclay, Kremlin Bicetre, France; INSERM U1030, Molecular Radiotherapy, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: [email protected] FAU - Chargari, Cyrus AU - Chargari C AD - Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif 94800, France; Faculte de Medecine, Universite Paris-Saclay, Kremlin Bicetre, France; INSERM U1030, Molecular Radiotherapy, Gustave Roussy Cancer Campus, Villejuif, France; Institut de Recherche Biomedicale des Armees, Bretigny sur Orge, France. FAU - Deutsch, Eric AU - ...
Nagina immissiun dals suandants pollens:. ambrosia, assens, badugn, chastagner cultivà, dent-liun, fains, fau, fau coller, fegliascha, fraissen, furment, ierdi, nitscholer, ogn, papla, plantagen, platana, ruver, salesch, seghel, tigl, ulm. gievgia, ils 18 da schaner 2018, 06:00 , MeteoNews ...
Nagina immissiun dals suandants pollens:. ambrosia, assens, badugn, chastagner cultivà, dent-liun, fains, fau, fau coller, fegliascha, fraissen, furment, ierdi, nitscholer, ogn, papla, plantagen, platana, ruver, salesch, seghel, tigl, ulm. gievgia, ils 18 da schaner 2018, 06:00 , MeteoNews ...
There are certain points in your life when words simply dont do justice to a situation. This is one of those times, thanks to new Florida Atlantic head coach Lane Kiffin and this (ahem) hype video. Commit to the Owls! Coach @Lane_Kiffin is bringing in the best recruits.
gil54 vende allasta al prezzo di 8,00 € fino al domenica 5 maggio 2019 17:23:00 CEST un oggetto nella categoria Avvisi di necrologio di Delcampe
chemBlink provides information about CAS # 1158728-82-5, 4-C-Azido-2-deoxy-2,2-difluorouridine, molecular formula: C9H9F2N5O5.
Νεαρός και ενώ έκανε τα πρώτα του βήματα στον επαγγελματικό χώρο των γραφιστών, εργαζόμενος συν τοις άλλοις στα έντυπα Hechos, La Ma ana και El Pa s, συνδέθηκε με την ROE (Resistencia Obrero Estudiantil - Αντίσταση Εργατών Σπουδαστών). Έγινε μέλος της FAU λίγο μετά αφότου προσέγγισε τον αναρχισμό. Anarkismo.net is an anarchist publishing project composed of groups who agree with the Anarkismo statement Anarkismo.net is a international anarchist-communist news service
Νεαρός και ενώ έκανε τα πρώτα του βήματα στον επαγγελματικό χώρο των γραφιστών, εργαζόμενος συν τοις άλλοις στα έντυπα Hechos, La Ma ana και El Pa s, συνδέθηκε με την ROE (Resistencia Obrero Estudiantil - Αντίσταση Εργατών Σπουδαστών). Έγινε μέλος της FAU λίγο μετά αφότου προσέγγισε τον αναρχισμό. Anarkismo.net is an anarchist publishing project composed of groups who agree with the Anarkismo statement Anarkismo.net is a international anarchist-communist news service
In his first radio interview since being fired, Pelini threatens legal action against affiants, alleges FAU AD Pat Chun had an agenda against him.
based on unique biological properties of 1-β-D-arabinofuranosyluracil (ara-U). More specifically some of its important ... O-anhydro-1-β-D-arabinofuranosyluracil (anhydro-ara-U); and acid-hydrolysis of anhydro-ara-U giving ara-U; and subsequent ...
... deoxy-5-iodo-1-beta-D-arabinofuranosyluracil in cardiac cells after adenoviral transfer of the herpesvirus thymidine kinase ...
... arabinofuranosyluracil MeSH D13.570.685.852.176 - azauridine MeSH D13.570.685.852.250 - 3-deazauridine MeSH D13.570.685.852.300 ... arabinofuranosyluracil MeSH D13.570.065.300 - cytarabine MeSH D13.570.065.300.050 - ancitabine MeSH D13.570.065.950 - ...
Arabinofuranosyluracil / adverse effects * Arabinofuranosyluracil / analogs & derivatives* * Arabinofuranosyluracil / ...
14C-2′-Fluoro-5-methyl-1-β-d-arabinofuranosyluracil (FIAU; specific activity 2 GBq/μmol) was obtained commercially (Hartmann ... Uptake of radiolabeled 2′-fluoro-2′-deoxy-5-iodo-1-β-D-arabinofuranosyluracil (FIAU) in cardiac cells after adenoviral transfer ... d-arabinofuranosyluracil (FIAU) and 9-(4-18F-fluoro-3-hydroxymethylbutyl)guanine (FHBG) as reporter probes, and secretion of ...
Cytarabine: Metabolized by cytidine deaminase to inactive metabolite 1-β-D-arabinofuranosyluracil (AraU) ...
based on unique biological properties of 1-β-D-arabinofuranosyluracil (ara-U). More specifically some of its important ... O-anhydro-1-β-D-arabinofuranosyluracil (anhydro-ara-U); and acid-hydrolysis of anhydro-ara-U giving ara-U; and subsequent ...
18F-fluoro-5-ethyl-1-β-D-arabinofuranosyluracil (27,28). Although these systems circumvent the shortcomings of their ...
Synthesis of guanylyl-(3→5)-uridylyl-(3→5)-arabinofuranosyluracil and guanylyl-(3→5)-uridylyl-(3→5)-arabino ...
... and 1-β-D-arabinofuranosyluracil, and of thymidine Nucleosides and Nucleotides. 15: 1041-1057. DOI: 10.1080/07328319608002033 ...
2-anhydro(1-.beta.-d-arabinofuranosyl)uracil. *2, 2-anhydrouridine. *2,2-o-cyclouridine ...
Synthesis of guanylyl-(3→5)-uridylyl-(3→5)-arabinofuranosyluracil and guanylyl-(3→5)-uridylyl-(3→5)-arabino ...
For example, the substrate 124I-fluoro-5-iodo-1-β-d-arabinofuranosyluracil can be used for quantification of viral thymidine ...
NU009 5-Fluoro-1-(2′-deoxy-2′-fluoro-3′,5′-di-O-benzoyl-β-L-arabinofuranosyl)-uracil From £119.00. - £664.00. exc. VAT ... NU006 1-(2′-Deoxy-2′-fluoro-3′-O-mesyl-5′-O-trityl-β-L-arabinofuranosyl)-uracil From £119.00. - £664.00. exc. VAT ... NU008 1-(2′-deoxy-2′-fluoro-3′,5′-di-O-benzoyl-β-L-arabinofuranosyl)-uracil From £92.00. - £544.00. exc. VAT ... NU007 1-(2′-Deoxy-2′-fluoro-5′-O-trityl-β-L-arabinofuranosyl)-uracil From £106.00. - £604.00. exc. VAT ...
Because cerebrospinal fluid levels of deaminase are low, little conversion to 1-β-D-arabinofuranosyluracil was observed. ... more than 80 percent of plasma radioactivity can be accounted for by the inactive metabolite 1-β-D-arabinofuranosyluracil. ... approximately 90 percent of which is excreted as 1-β-D-arabinofuranosyluracil. ...
... beta-D-arabinofuranosyluracil (FMAU). FMAU is a thymidine analog that is phosphorylated by both cytosolic thymidine kinase 1 ( ...
McMahon M, Contreras A, Holm M, Uechi T, Forester CM, Pang X, Jackson C, Calvert ME, Chen B, Quigley DA, Luk JM, Kelley RK, Gordan JD, Gill RM, Blanchard SC, Ruggero D. A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS. Elife. 2019 09 03; 8 ...
... fluoro-5-methyl-1-Beta-D-arabinofuranosyluracil (FMAU), and analogs with a longer half-life, such as iodine-124 iodo-2´- ...
Burd A, Levine RL, Ruppert AS, Mims AS, Borate U, Stein EM, Patel P, Baer MR, Stock W, Deininger M, Blum W, Schiller G, Olin R, Litzow M, Foran J, Lin TL, Ball B, Boyiadzis M, Traer E, Odenike O, Arellano M, Walker A, Duong VH, Kovacsovics T, Collins R, Shoben AB, Heerema NA, Foster MC, Vergilio JA, Brennan T, Vietz C, Severson E, Miller M, Rosenberg L, Marcus S, Yocum A, Chen T, Stefanos M, Druker B, Byrd JC. Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial. Nat Med. 2020 12; 26(12):1852-1858 ...
Synthesis of 2-deoxy-2-[.sup.18F]fluoro-5-methyl-1-B-D-arabinofuranosyluracil (.sup.18F-FMAU) Patent Li, Zibo; Cai, Hancheng ...
Arabinofuranosyluracil / analogs & derivatives Actions. * Search in PubMed * Search in MeSH * Add to Search ...
Arabinofuranosyluracil / adverse effects Actions. * Search in PubMed * Search in MeSH * Add to Search ...
Cytarabine is metabolized by cytidine deaminase to the inactive metabolite 1-β-D-arabinofuranosyluracil (AraU). ...
2-fluoro-5-methyl-beta-L-arabinofuranosyl] uracil), a potent inhibitor of HBV replication in the woodchuck model of hepatitis B ...
19F NMR Study of the Uptake of 2′-Fluoro-5-methyl-β-l-arabinofuranosyluracil in Erythrocytes: Evidence of Transport by ... 19F NMR Study of the Uptake of 2′-Fluoro-5-methyl-β-l-arabinofuranosyluracil in Erythrocytes: Evidence of Transport by ...
1-beta-D-Arabinofuranosyl Uracil Term UI T003296. Date11/20/1980. LexicalTag NON. ThesaurusID UNK (19XX). ... Arabinofuranosyluracil Preferred Term Term UI T003298. Date01/01/1999. LexicalTag NON. ThesaurusID NLM (1976). ... Arabinofuranosyluracil. Tree Number(s). D03.383.742.680.852.150. D13.570.065.090. D13.570.685.852.150. Unique ID. D001086. RDF ... Arabinofuranosyluracil Preferred Concept UI. M0001641. Registry Number. 3083-77-0. Scope Note. A pyrimidine nucleoside formed ...
1-β-d-arabinofuranosyluracil [ara-U, uracil arabinoside]) in plasma. ...
Synthesis and Evaluation of 2′-Deoxy-2′-18F-Fluoro-5-Fluoro-1-β-d-Arabinofuranosyluracil as a Potential PET Imaging Agent for ...
1-beta-D-Arabinofuranosyl Uracil Term UI T003296. Date11/20/1980. LexicalTag NON. ThesaurusID UNK (19XX). ... Arabinofuranosyluracil Preferred Term Term UI T003298. Date01/01/1999. LexicalTag NON. ThesaurusID NLM (1976). ... Arabinofuranosyluracil. Tree Number(s). D03.383.742.680.852.150. D13.570.065.090. D13.570.685.852.150. Unique ID. D001086. RDF ... Arabinofuranosyluracil Preferred Concept UI. M0001641. Registry Number. 3083-77-0. Scope Note. A pyrimidine nucleoside formed ...
Sofosbuvir Impurity SA15418; 1-β-D-Arabinofuranosyluracil-2-C-methyl. CAS No.. : 114262-49-6. ...
... monomethylether disinfecting scotoma stxbp1 erotica lithocholic thickening agitated soleirolii hippurus arabinofuranosyluracil ...
Ara U is an acronym for Arabinofuranosyluracil. ara-C is an abbreviation of 1-beta-D-arabiofuranosylcytosine. ara-C is an ...
D-ARABINOFURANOSYL)URACIL C80036 3VSI4D701X 1-(PHENYLAZO)-2-NAPHTHYLAMINE C80141 X2I96B6OVW 1,1,2,2-TETRAFLUOROETHANE C77540 ...
6. 2-Fluoro-5-([11C]-methyl)-1-β-D-arabinofuranosyluracil. Chopra A. Molecular Imaging and Contrast Agent Database [Internet ...
1- (2-Deoxy-2-fluoro-β -D-arabinofuranosyl) uracil (2 -FANA-U) Quick inquiry Where to buy ... 1- (2-Deoxy-2-fluoro-β -D-arabinofuranosyl) uracil (2 -FANA-U). Uses: Laboratory. Grades: Laboratory.. ...
D3.383.742.686.246.50 Arabinofuranosyluracil D3.383.742.680.852.150 Archives K1.504.152 K1.400.152 Argipressin D6.472.699.976. ...
... nucleoside arabinofuranosylpurine nucleosides arabinofuranosylpurines arabinofuranosylthymine arabinofuranosyluracil ...
... l-arabinofuranosyl) uracil] shows powerful activity against HBV in HepG2.2.15 cells (11) and in clinical trials (2, 6, 11), but ...
1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl) uracil. *1-Docosanol. *1-methyl-d-tryptophan ...
Glycerate 1,3-bisphosphate + 2-Fluoro-5-methyl-beta-D-arabinofuranosyluracil-diphosphate <-> Glycerate 3-phosphate + 2-Fluoro ... Glycerate 1,3-bisphosphate + 2-Fluoro-5-methyl-beta-L-arabinofuranosyluracil-diphosphate <-> Glycerate 3-phosphate + 2-Fluoro ... methyl-beta-D-arabinofuranosyluracil-triphosphate 3-Deoxy-3-fluoro-D-glucose 6-phosphate <-> 3-Deoxy-3-fluoro-D-fructose 6- ...
Inhibitory effect of 2-fluoro-5-methyl-beta-L-arabinofuranosyl-uracil on duck hepatitis B virus replication. ...
5-Fluoro-1-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-β-L-arabinofuranosyl)-uracil Product details ... 1-(2-Deoxy-2-fluoro-3-O-mesyl-5-O-trityl-β-L-arabinofuranosyl)-uracil Product details ... 1-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-β-L-arabinofuranosyl)-uracil Product details ... 1-(2-Deoxy-2-fluoro-5-O-trityl-β-L-arabinofuranosyl)-uracil Product details ...
Arabinofuranosyluracil Arabinonucleosides Arabinonucleotides Arabinose Arabis Arabs AraC Transcription Factor Araceae ...
2-Deoxy-2-[18F]fluoro-5-methyl-β-l-arabinofuranosyluracil (l-[18F]FMAU) and 2-deoxy-2-[18F]fluoro-β-d-arabinofuranosylcytosine ...
  • Our group has extensive expertise in the clinical evaluation of an emerging PET tracer known as 18F-2'-fluoro-5-methyl-1- beta-D-arabinofuranosyluracil (FMAU). (usc.edu)