| 1. |
- Hu, Jinhong, et al.
(author)
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Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults
- 2008
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In: PLOS ONE. - : PLOS. - 1932-6203. ; 3:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: The P. falciparum chimeric protein 2.9 (PfCP-2.9) consisting of the sequences of MSP1-19 and AMA-1 (III) is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 microg respectively, and 1 placebo group of 12 participants receiving the adjuvant only.METHODS AND FINDINGS: The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs) was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1:10,000) of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA).CONCLUSION: This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested) and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity.TRIAL REGISTRATION: Chinese State Food and Drug Administration (SFDA) 2002SL0046; Controlled-Trials.com ISRCTN66850051 [66850051].
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| 2. |
- Liu, X. E., et al.
(author)
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A novel ruthenium(II) tris(bipyridine)-zinc porphyrin-rhenium carbonyl triad : synthesis and optical properties
- 2006
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In: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 62:15, s. 3674-3680
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Journal article (peer-reviewed)abstract
- A novel ruthenium(II) tris(bipyridine)-zinc porphyrin-rhenium carbonyl triads and its free base porphyrin derivative were synthesized and characterized by H-1, C-13 NMR, UV-vis, mass-spectrometry and elemental analysis. The redox potentials of the two Compounds were measured and compared to their corresponding reference complexes. The fluorescence and transient absorption spectra of the two complexes revealed the features of two different pathways for possible photoinduced intramolectular electron transfer or energy transfer in the triads.
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| 3. |
- Liu, Xien, et al.
(author)
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Synthesis, electrochemical, and photophysical studies of multicomponent systems based on porphyrin and ruthenium(II) polypyridine complexes
- 2007
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In: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 63:37, s. 9195-9205
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Journal article (peer-reviewed)abstract
- Two ruthenium tris-bipyridine functionalized porphyrins 4, 8 and their Zn derivatives 4-Zn, 8-Zn were designed, synthesized, and characterized. The redox potentials of these complexes as well as their corresponding monomeric reference porphyrin and ruthenium bipyridine complexes were also measured for comparison. Primary dynamic studies on the electron injection and backing recombination between these complexes and TiO2 nanoparticles were carried out by means of transient absorption spectroscopy. The results indicate that a long-lived charge separation state was obtained in these assemblies.
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| 4. |
- Schael, S, et al.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Research review (peer-reviewed)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 5. |
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| 6. |
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| 7. |
- Kotnis, A, et al.
(author)
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Non-homologous end joining in class switch recombination: the beginning of the end
- 2009
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In: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. - : The Royal Society. - 1471-2970. ; 364:1517, s. 653-665
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Journal article (peer-reviewed)abstract
- Immunoglobulin class switch recombination (CSR) is initiated by a B-cell-specific factor, activation-induced deaminase, probably through deamination of deoxycytidine residues within the switch (S) regions. The initial lesions in the S regions are subsequently processed, resulting in the production of DNA double-strand breaks (DSBs). These breaks will then be recognized, edited and repaired, finally leading to the recombination of the two S regions. Two major repair pathways have been implicated in CSR, the predominant non-homologous end joining (NHEJ) and the alternative end-joining (A-EJ) pathways. The former requires not only components of the ‘classical’ NHEJ machinery, i.e. Ku70/Ku80, DNA-dependent protein kinase catalytic subunit, DNA ligase IV and XRCC4, but also a number of DNA-damage sensors or adaptors, such as ataxia–telangiectasia mutated, γH2AX, 53BP1, MDC1, the Mre11–Rad50–NBS1 complex and the ataxia telangiectasia and Rad3-related protein (ATR). The latter pathway is not well characterized yet and probably requires microhomologies. In this review, we will focus on the current knowledge of the predominant NHEJ pathway in CSR and will also give a perspective on the A-EJ pathway.
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| 8. |
- Li, Minna, et al.
(author)
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Oligo thiophene-2-yl-vinyl bridged mono- and binuclear ruthenium(II) tris-bipyridine complexes : Synthesis, photophysics, electrochemistry and electrogenerated chemiluminescence
- 2008
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In: Journal of Organometallic Chemistry. - : Elsevier BV. - 0022-328X .- 1872-8561. ; 693:1, s. 46-56
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Journal article (peer-reviewed)abstract
- A series of mono- and binuclear ruthenium(II) tris-bipyridine complexes tethered to oligothienylenevinyleries have been synthesized and characterized by H-1 NMR, C-13 NMR and TOF-MS spectrometry. Photophysics, electrochemistry and electrogenerated chemiluminescence (ECL) properties of these complexes are investigated. The electronic absorption spectra of the mononuclear ruthenium complexes show a significant red shift both at MLCT (metal-to-ligand charge transfer) and pi-pi* transitions of oligothienylenevinylenes with increase in the number of thiophenyl-2-yl-vinyl unit. For the binuclear complexes these two absorption bands are overlapped.) All the metal complexes have very weak emission compared to that of the reference complex Ru(bpy)(3)(2+). The first reduction potentials of all mononuclear ruthenium complexes are less negative than that of Ru(bpy)(3)(2+), due to the moderate electron-withdrawing effect of oligothienylenevinylenes. For binuclear ruthenium complexes, only one Ru(II/III) oxidation peak (E-1/2=0.96V vs. Ag/Ag+) was observed, suggesting a weak interaction between two metal centers. Three successive reduction processes of bipyridine ligands are similar among all ruthenium complexes except for RuTRu, which has a very sharp peak owing to the accumulation of neutral product oil the electrode surface. All these ruthenium complexes exhibited different ECL property in CH3CN solution without any additional reductant or oxidant. For three mononuclear ruthenium complexes, the ECL intensity strengthens with increase in the number of thiophene-2-yl-vinyl unit. However, the ECL efficiency dramatically decreased in the binuclear ruthenium complexes. The ECL efficiencies of all the)2+, reported complexes do not exceed that of Ru(bpy 3 where the ECL efficiency decreases in the order of RuTRu > Ru3T > Ru2T > RuT > Ru2TRu (RuT, bis-2,2'-bipyridyl-(4-metliyl-4'-(2-thienylethenyl)-2,2'-bipyridine) ruthenium dihexafluorophosphate; Ru2T, bis-2,2'-bipyridyl-(4-methyl-4'-{(E) -2-[5-((E) -2-thienylethenyl)-thienylethenyl])-2,2'-bipyridine)ruthenium dihexafluorophosphate; Ru3T, bis-2,2'-bipyridyl-(4-methyl-4'-[(E)-2-{(E)-2-[5-((E)-2-thienylethenyl)- thienylethenyl])}-2,2'-bipyridine) ruthenium dihexafluorophosphate; RuTRu, bis-2,2'-bipyridyl-ruthenium-bis-[2-((E)-4'-methyl-2,2'-bipyridinyl-4)-e thenyl]-thienyl-bis-2,2'-bipyridyl-ruthenium tetrahexafluorophosphate; Ru2TRu, bis-2,2'-bipyridyl-ruthenium-(E)-1,2-bis-{2-[2-((E)-4'-methyl-2,2'-bipyr idinyl-4)-ethenyl]-thienyl}ethenyl-bis-2,2'-bipyridyl-ruthenium tetrahexafluorophosphate).
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| 9. |
- Li, Xueqiang, et al.
(author)
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Noncovalent assembly of a metalloporphyrin and an iron hydrogenase active-site model : Photo-induced electron transfer and hydrogen generation
- 2008
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207 .- 1089-5647. ; 112:27, s. 8198-8202
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Journal article (peer-reviewed)abstract
- A noncovalent assembly of a pyridyl-functionalized hydrogenase active-site model complex and zinc tetraphenylporphyrin has been obtained and characterized. Upon light irradiation, fluorescence quenching by electron transfer was observed from the singlet excited state of the porphyrin to the diiron center, and the mechanism was verified by fluorescence lifetime and transient absorption spectroscopic measurements. In contrast to molecular dyads linked by covalent bonds, the assembled system was designed to avoid charge recombination via complex dissociation after photo-induced electron transfer. Visible light-driven hydrogen generation was observed from this self-assembled system. The assembling strategy employed in this study has the potential to be used for any other hydrogenase models in the future.
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| 10. |
- Liu, Bilong, 1970-
(author)
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Acoustical Characteristics of Aircraft Panels
- 2006
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Doctoral thesis (other academic/artistic)abstract
- A deterministic approach based on a modal expansion and modal receptance method has been developed to evaluate the airborne sound insulation of aircraft panels with stringer and ring frame attachments. Furthermore, this method was extended to predict the noise radiation of stiffening panel subjected to TBL excitation. This approach integrates with the fast and accurate methods in evaluating the modal excitation terms and modal radiation efficiency. Based on these advantages, the effects of the curvature, overpressure, stringers, ring frames, hydrodynamic coincidence, composite structures and structural dissipation on the acoustical properties of a typical aircraft panel are able to be investigated efficiently.Theoretic predictions were compared with laboratory measurements conducted on both model structures and aircraft panels. It was found that a small curvature may result in significant deterioration of the sound transmission loss at frequencies of interest. Unlike a flat uniform panel, the theoretical prediction for curved panels from the infinite model can not provide good agreement with the measurement close to and well below the ring frequency. However, in this frequency range, the finite model has been proved to be applicableFor the large curved airplane panels studied here, it was found that the ring frames have little influence on sound transmission loss in the frequency range of interest. However the stringers may have considerable influence on sound transmission loss. The stringer improves this for a curved panel around the ring frequency, but it may result in a potential deterioration of the sound transmission loss above the ring frequency. In this study it is evident that the sound transmission loss of the composite skin attached with composite stringers is lower than that of the metallic panel attached with metallic stringers.At frequencies higher than the corresponding ring frequency of the curved panel, both experiment and theoretical prediction reveal that the overpressure at the concave side tends to reduce the sound transmission loss at the rate of about 0.5dB /10000 Pa. While at lower frequencies, say well below the ring frequency, the overpressure may increase or reduce sound transmission loss of a finite panel, depending on the shift of the resonant frequencies resulting from the overpressure.For TBL excitation, numerical investigation reveals that the panel with the ring frames behaves more like a sub-panel between two frames. Below 500Hz, the ring frames slightly enhance the sound radiation while dramatically increasing it around 1.3kHz. The TBL forcing field excites the same vibration lever for the panel with and without ring frame attachments, but the modes excited for the panel with ring frames radiate more sound. Unlike the ring frames, the stringers increase sound radiation below 1kHz. Above 1kHz, the sub-panels between two bays respond independently and the stringer effects is therefore not obvious.
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