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• 1
Description: In this work we construct uniform asymptotic expansion of $\sn(t|m)$ - Jacobi when $m\to1-0$. The constructed expansion is valid over more than a half of period. The turning point is included into the interval of validity for the approximation. In addition we obtain the asymptotic formula for elliptic integral of the first kind and discuss the differences with the same formula from a handbook. Comment: 9 pages, 5 figures
Keywords: Mathematics - Classical Analysis And Odes ; Nonlinear Sciences - Exactly Solvable And Integrable Systems
Source: Cornell University
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• 2
Article
Language: English
In: Bioorganic & Medicinal Chemistry, 15 December 2014, Vol.22(24), pp.6826-6836
Description: Influenza virus is serious human pathogen leading to high morbidity and mortality all over the world. Due to high rate of mutation, it is able to fast development of drug resistance that makes necessary to search novel antivirals with broad range and alternative targets. In the present study we describe synthesis and anti-viral activity of novel derivatives of usnic acid (2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyl-1,3(2 ,9b )-dibenzo-furandione). It is shown that anti-viral activity of usnic acid can be increased by side moieties introduction. The modification with chalcones appeared to be the most effective. Our study revealed that (−)-usnic acid exhibited higher antiviral activity than its (+)-enantiomer, but in the pairs of enantiomer derivatives such as enamines, pyrazoles and chalcones, the (+)-enantiomers were more potent inhibitors of the virus. For other groups of compounds the inhibiting activities of the enantiomers were comparable. Further optimization of the structure could therefore result in development of novel anti-influenza compound with alternative target and mechanism of virus-inhibiting action.
Keywords: Usnic Acid ; Usnic Acid Derivatives ; Influenza ; Anti-Viral Activity ; Medicine ; Chemistry ; Anatomy & Physiology
ISSN: 0968-0896
E-ISSN: 1464-3391
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• 3
Article
Language: English
In: Letters in Drug Design & Discovery, 2011, Vol.8(4), p.375-380
Description: A number of new derivatives of monoterpenoid with a para-menthane framework 3-methyl-6-(prop-1-en-2- yl)cyclohex-3-ene-1,2-diol (-)-3 were synthesized. The antiviral activity of (-)-3 and its derivatives against the pandemic influenza virus A/California/07/09 (H1N1)v was studied in vitro. Compound (-)-3 was found to be active against this virus (selectivity index 7.5); for mononicotinate (+)-6 the selectivity index was 17. The absolute configuration of compound 6 was shown to be critical for its antiviral activity.
Keywords: Monoterpenoids ; Para-Menthane ; Nicotinate ; Influenza ; Pandemic ; Antiviral ; Chemotherapy Drugs ; Influenza Epidemics ; Antiviral Chemotherapy ; Melaleuca Armillars ; Methane Series ; Anticonvulsant ; Anti Parkinsonians Activiies ; Isonicotinoyl Chloride Hydrochloride, ; Chicken Embryos ; Erythrocytes
ISSN: 1570-1808
E-ISSN: 1875-628X
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• 4
Article
Language: English
In: Journal of Mathematical Physics, June 2014, Vol.55(6)
Description: The subject of this paper is solutions of an autoresonance equation. We look for a connection between the parameters of the solution bounded as t   →−∞, and the parameters of two two-parameter families of solutions as t   → ∞. One family consists of the solutions which are not captured into resonance, and another of those increasing solutions which are captured into resonance. In this way we describe the transition through the separatrix for equations with slowly varying parameters and get an estimate for parameters before the resonance of those solutions which may be captured into autoresonance.
Keywords: Articles
ISSN: 0022-2488
E-ISSN: 1089-7658
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• 5
Article
Language: English
In: Bioorganic & Medicinal Chemistry, 01 April 2014, Vol.22(7), pp.2141-2148
Description: Influenza is a continuing world-wide public health problem that causes significant morbidity and mortality during seasonal epidemics and sporadic pandemics. The purpose of the study was synthesis and investigation of antiviral activity of camphor-based symmetric diimines and diamines. A set of C2-symmetric nitrogen-containing camphor derivatives have been synthesized. The antiviral activity of these compounds was studied against rimantadine- and amantadine-resistant influenza virus A/California/7/09 (H1N1)pdm09 in MDCK cells. The highest efficacy in virus inhibiting was shown for compounds – with cage moieties bound by aliphatic linkers. The therapeutic index (selectivity index) for exceeded that for reference compounds amantadine, deitiforin and rimantadine almost 10-fold. As shown by structure–activity analysis, the length of the linker has a dramatic effect on the toxicity of compounds. Compound with –C H – linker exhibited the lowest toxicity (CTD = 2216 μM). Derivatives of camphor, therefore, can be considered as prospective antiinfluenza compounds active against influenza viruses resistant to adamantane-based drugs.
Keywords: Camphor ; Diimine Derivatives ; Antivirals ; Influenza ; Medicine ; Chemistry ; Anatomy & Physiology
ISSN: 0968-0896
E-ISSN: 1464-3391
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• 6
Article
Language: English
In: PLoS ONE, 2011, Vol.6(4), p.e18577
Description: H5N1 influenza vaccines, including live intranasal, appear to be relatively less immunogenic compared to seasonal analogs. The main influenza virus surface glycoprotein hemagglutinin (HA) of highly pathogenic avian influenza viruses (HPAIV) was shown to be more susceptible to acidic pH treatment than that of human or low pathogenic avian influenza viruses. The acidification machinery of the human nasal passageway in response to different irritation factors starts to release protons acidifying the mucosal surface (down to pH of 5.2). We hypothesized that the sensitivity of H5 HA to the acidic environment might be the reason for the low infectivity and immunogenicity of intranasal H5N1 vaccines for mammals. ; We demonstrate that original human influenza viruses infect primary human nasal epithelial cells at acidic pH (down to 5.4), whereas H5N1 HPAIVs lose infectivity at pH≤5.6. The HA of A/Vietnam/1203/04 was modified by introducing the single substitution HA2 58K→I, decreasing the pH of the HA conformational change. The H5N1 reassortants containing the indicated mutation displayed an increased resistance to acidic pH and high temperature treatment compared to those lacking modification. The mutation ensured a higher viral uptake as shown by immunohistochemistry in the respiratory tract of mice and 25 times lower mouse infectious dose. Moreover, the reassortants keeping 58K→I mutation designed as a live attenuated vaccine candidate lacking an NS1 gene induced superior systemic and local antibody response after the intranasal immunization of mice. ; Our finding suggests that an efficient intranasal vaccination with a live attenuated H5N1 virus may require a certain level of pH and temperature stability of HA in order to achieve an optimal virus uptake by the nasal epithelial cells and induce a sufficient immune response. The pH of the activation of the H5 HA protein may play a substantial role in the infectivity of HPAIVs for mammals.
Keywords: Research Article ; Biology ; Medicine ; Virology ; Immunology ; Infectious Diseases
E-ISSN: 1932-6203
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• 7
Article
Language: English
In: Nuclear Instruments and Methods in Physics Research, A, Oct 1, 2015, Vol.796, p.158(7)
Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.nima.2015.05.022 Byline: Vladimir Eremin, Oleg Kiselev, Nicolai Egorov, Igor Eremin, Yuri Tuboltsev, Elena Verbitskaya, Andrei Gorbatyuk Abstract: Construction of new accelerating facilities to investigate reactions with heavy ions requires upgrading of the Time-of-Flight (TOF) systems for on-line ion identification. The requested time resolution of the TOF system developed for Super FRagment Separator in the frame of the FAIR program at GSI, Germany, is in the range of tens of picoseconds, which can be realized by using planar silicon detectors. Such resolution will allow characterization of relativistic ions from Lithium to Uranium. However, fast timing of heavy ions with semiconductor detectors is expected to be limited by the so-called plasma effect due to a high concentration of electron-hole pairs in tracks. Here the results of the experiment with relativistic.sup.197Au ions (the energy of 920MeV per nucleon) obtained with Si detectors are described, which showed the TOF time resolution around 14psrms. The physical mechanism of charge collection from high-density penetrating tracks of relativistic heavy ions is considered and the analysis of timing characteristics is performed taking into account track polarization. Polarization is shown to have a strong influence on the formation of the leading edge of the detector current response generated by relativistic heavy ions, which allows us to explain the observed high time resolution. Author Affiliation: (a) Ioffe Institute, 26 Politekhnicheskaya Street, St. Petersburg 194021, Russian Federation (b) GSI Helmholtzzentrum fur Schwerionenforschung, Planenstrasse 1, Darmstadt D-64291, Germany (c) Research Institute of Material Science and Technology, 4 Passage 4806, Moscow, Zelenograd 124460, Russian Federation Article History: Received 15 November 2014; Revised 10 May 2015; Accepted 11 May 2015
Keywords: Detection Equipment – Analysis
ISSN: 0168-9002
Source: Cengage Learning, Inc.
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• 8
Article
In: PLoS ONE, 2014, Vol.9(2)
Description: Introduction Live attenuated influenza vaccines (LAIVs) are being developed to protect humans against future epidemics and pandemics. This study describes the results of a double–blinded randomized placebo–controlled phase I clinical trial of cold–adapted and temperature sensitive H7N3 live attenuated influenza vaccine candidate in healthy seronegative adults. Objective The goal of the study was to evaluate the safety, tolerability, immunogenicity and potential shedding and transmission of H7N3 LAIV against H7 avian influenza virus of pandemic potential. Methods and Findings Two doses of H7N3 LAIV or placebo were administered to 40 randomly divided subjects (30 received vaccine and 10 placebo). The presence of influenza A virus RNA in nasal swabs was detected in 60.0% and 51.7% of subjects after the first and second vaccination, respectively. In addition, vaccine virus was not detected among placebo recipients demonstrating the absence of person–to–person transmission. The H7N3 live attenuated influenza vaccine demonstrated a good safety profile and was well tolerated. The two–dose immunization resulted in measurable serum and local antibody production and in generation of antigen–specific CD4 + and CD8 + memory T cells. Composite analysis of the immune response which included hemagglutinin inhibition assay, microneutralization tests, and measures of IgG and IgA and virus–specific T cells showed that the majority (86.2%) of vaccine recipients developed serum and/or local antibodies responses and generated CD4 + and CD8 + memory T cells. Conclusions The H7N3 LAIV was safe and well tolerated, immunogenic in healthy seronegative adults and elicited production of antibodies broadly reactive against the newly emerged H7N9 avian influenza virus. Trial registration ClinicalTrials.gov NCT01511419
Keywords: Research Article ; Biology ; Medicine
E-ISSN: 1932-6203
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• 9
Article
Language: English
In: PLoS ONE, 01 January 2015, Vol.10(3), p.e0119520
Description: Matrix 2 protein ectodomain (M2e) is considered a promising candidate for a broadly protective influenza vaccine. M2e-based vaccines against human influenza A provide only partial protection against avian influenza viruses because of differences...
Keywords: Sciences (General)
E-ISSN: 1932-6203
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• 10
Article
Language: English
In: Bioorganic & Medicinal Chemistry, 2010, Vol.18(2), pp.839-848
Description: Chemotherapy and chemoprophylaxis of influenza is one of the most important directions of health protection activity. Due to the high rate of drug-resistant strains of influenza virus, there is a need for the search and further development of new potent antivirals against influenza with a broad spectrum of activity. In the present study, a set of di-, tri- and tetrazole derivatives of adamantane was efficiently prepared and their anti-influenza activities evaluated against rimantadine-resistant strain A/Puerto Rico/8/34. In general, derivatives of tetrazole possessed the highest virus-inhibiting activity. We demonstrated that several compounds of this set exhibited much higher activity than the currently used antiviral rimantadine, a compound of related structure. Moreover, we showed that these azolo-adamantanes were significantly less toxic. This study demonstrates that influenza viruses can be inhibited by adamantyl-azoles and thus have potential for developing antiviral agents with an alternate mechanism of action.
Keywords: Azoles ; Adamantane Derivatives ; Influenza Virus ; Antivirals ; Medicine ; Chemistry ; Anatomy & Physiology
ISSN: 0968-0896
E-ISSN: 1464-3391
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