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- Hagiwara, K, et al.
(författare)
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Review of particle physics
- 2002
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Ingår i: Physical Review D (Particles and Fields). - 0556-2821. ; 66:1
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Forskningsöversikt (refereegranskat)abstract
- This biennial Review summarizes much of Particle Physics Using data from previous editions, plus 2205 new measurements from 667 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles All the particle properties and search limits are listed in Summary Tables We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics This edition features expanded coverage of CP violation in B mesons and of neutrino oscillations For the first time we cover searches for evidence of extra dimensions (both in the particle listings and in a new review) Another new review is on Grand Unified Theories A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review All tables, listings, and reviews (and errata) are also available on the Particle Data Group website http //pdg 1b1 gov.
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| 2. |
- Andersson, H.O., et al.
(författare)
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Optimization of P1-P3 groups in symmetric and asymmetric HIV-1 protease inhibitors
- 2003
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 270:8, s. 1746-1758
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 protease is an important target for treatment of AIDS, and efficient drugs have been developed. However, the resistance and negative side effects of the current drugs has necessitated the development of new compounds with different binding patterns. In this study, nine C-terminally duplicated HIV-1 protease inhibitors were cocrystallised with the enzyme, the crystal structures analysed at 1.8-2.3 Å resolution, and the inhibitory activity of the compounds characterized in order to evaluate the effects of the individual modifications. These compounds comprise two central hydroxy groups that mimic the geminal hydroxy groups of a cleavage-reaction intermediate. One of the hydroxy groups is located between the d-oxygen atoms of the two catalytic aspartic acid residues, and the other in the gauche position relative to the first. The asymmetric binding of the two central inhibitory hydroxyls induced a small deviation from exact C2 symmetry in the whole enzyme-inhibitor complex. The study shows that the protease molecule could accommodate its structure to different sizes of the P2/P2' groups. The structural alterations were, however, relatively conservative and limited. The binding capacity of the S3/S3' sites was exploited by elongation of the compounds with groups in the P3/P3' positions or by extension of the P1/P1' groups. Furthermore, water molecules were shown to be important binding links between the protease and the inhibitors. This study produced a number of inhibitors with Ki values in the 100 picomolar range.
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| 3. |
- Wan, Y., et al.
(författare)
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Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist
- 2004
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Ingår i: J Med Chem. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 47:24, s. 5995-6008
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Tidskriftsartikel (refereegranskat)abstract
- The first druglike selective angiotensin II AT(2) receptor agonist (21) with a K(i) value of 0.4 nM for the AT(2) receptor and a K(i) > 10 microM for the AT(1) receptor is reported. Compound 21, with a bioavailability of 20-30% after oral administration and a half-life estimated to 4 h in rat, induces outgrowth of neurite cells, stimulates p42/p44(mapk), enhances in vivo duodenal alkaline secretion in Sprague-Dawley rats, and lowers the mean arterial blood pressure in anesthetized, spontaneously hypertensive rats. Thus, the peptidomimetic 21 exerts a similar biological response as the endogenous peptide angiotensin II after selective activation of the AT(2) receptor. Compound 21, derived from the prototype nonselective AT(1)/AT(2) receptor agonist L-162,313 will serve as a valuable research tool, enabling studies of the function of the AT(2) receptor in more detail.
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| 11. |
- Wan, Y., et al.
(författare)
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First reported nonpeptide AT1 receptor agonist (L-162,313) acts as an AT2 receptor agonist in vivo
- 2004
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Ingår i: J Med Chem. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 47:6, s. 1536-1546
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Tidskriftsartikel (refereegranskat)abstract
- In this investigation, it is demonstrated that the first nonpeptide AT(1) receptor agonist L-162,313 (1), disclosed in 1994, also acts as an agonist at the AT(2) receptor. In anesthetized rats, administration of compound 1 intravenously or locally in the duodenum increased duodenal mucosal alkaline secretion, effects that were sensitive to the selective AT(2) receptor antagonist PD-123,319. The data strongly suggest that 1 is an AT(2) receptor agonist in vivo. To the best of our knowledge, this substance is the first nonpeptidic low-molecular weight compound with an agonistic effect mediated through the AT(2) receptor.
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| 18. |
- Erdélyi, Máté, 1975-
(författare)
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Towards the Development of Photoswitchable β-Hairpin Mimetics
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peptide secondary structure mimetics are important tools in medicinal chemistry, as they provide analogues of endogeneous peptides with new physicochemical and pharmacological properties. The β-hairpin motif has been shown to be involved in numerous physiological processes, among others in regulation of eucariotic gene transcription. This thesis addresses the design, synthesis and conformational analysis of photoswitchable β-hairpin mimetics.The developmental work included the establishment of an improved procedure for cross coupling of aryl halides with terminal alkynes. Microwave mediated Sonogashira couplings in closed vessels were optimized under homogeneous and solid-phase conditions furnishing excellent yields for a large variety of substrates within 5 – 25 minutes. In addition, microwave heating was shown not to have any non-conventional effect on the reaction rate.Furthermore, the most important factors affecting β-hairpin stability were evaluated. Studies of tetrapeptide and decapeptide analogues revealed the essential role of the β-turn in initiation of hairpin folding. Moreover, hydrogen bonding was shown to be the main interchain stabilizing force, whereas hydrophobic interactions were found to be relatively weak. Nevertheless, hydrophobic packing appears to provide an important contribution to the thermodynamic stability of β-hairpins.Photoswitchable peptidomimetics were prepared by incorporation of various stilbene moieties into tetra- and decapeptides. Synthesis, photochemical isomerisation and spectroscopic conformational analysis of the compounds were performed.
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| 22. |
- Makitalo, B, et al.
(författare)
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Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen
- 2004
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 85:Pt 8, s. 2407-2419
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Tidskriftsartikel (refereegranskat)abstract
- The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIB env, gag, RT, rev, tat and nef, and MVA expressing HIV-1 IIIB nef, tat and rev and simian immunodeficiency virus (SIV) macJ5 gag/pol and vaccinia HIV-1 env, were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.m.) at month 0 and intrarectally (i.r.) and intra-orally (i.o.) at 2 months, followed by MVA i.m. at 4 months and i.r. and i.o. at 8 months. Another group of four monkeys received the same immunogens but only i.m.. Overall, stronger cellular immune responses measured by ELISPOT and T-cell proliferation assay were detected in the group primed i.m. and boosted mucosally. Following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, one of eight vaccinated animals was completely protected. This monkey, immunized i.m. and i.r.+i.o., exhibited the highest levels of HIV Env, Nef and Tat antibodies, high HIV Tat cytotoxic T-lymphocyte activity and T-lymphocyte proliferative responses to HIV Env. Four weeks post-challenge none of the monkeys immunized i.m. and i.r.+i.o., and only two out of four animals immunized i.m., demonstrated detectable plasma viral RNA levels. In contrast, all eight control animals had demonstrable plasma viral RNA levels 4 weeks post-challenge. Thus, stronger cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. as well as mucosally, compared with animals immunized i.m. only. The breadth and magnitude of the induced immune responses correlated with protective efficacy.
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- Rosqvist, G., et al.
(författare)
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Diatom oxygen isotopes in pro-galcial lake sediments from northern Sweden: A 5000 year record of atmospheric circulation.
- 2004
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 23:7-8, s. 851-859
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Tidskriftsartikel (refereegranskat)abstract
- We use a pro-glacial oxygen isotope record of diatom silica (δ18Odiatom) and a sedimentary proxy for glacier flutuations to determine centennial-millennial scale climate change during the last 5000 yeras in northern Sweden. We show that the lake water isotopic composition åredominantly reflects the isotopic composition of the precipitation. Superimposed on a general depletion trend of 3.5‰ over the past 5000 years we found that the isotopic composition of precipitation became depleted (> 1‰ excursions) during four occasions centered at 4400, 3000, 2000 and, after 1200 cal yr BP. Climate simultaneously sustained a positive glacier mass balance, taht caused the catchment glacier to advance. A peristan cgange in the atmopheric circulation pattern could potentially have caused the registered chnages in the δ18Odiatom because different air masses hold characteristics δ18O signatures of their precipitation. The glacier mass balance primarily responds to the influence of summer temperature on ablation. We suggest that the most likely cause for the recorded chnages in both these proxies is a steadily increasing but fluctuating dominance of colder and δ18O depleted air masses from the north/northeast during the past 5000 years. Theδ18Odiatom depletion and glacier events all occur at times of relative ice-rafted-debris maxima in the North Atlanic, consistent with cold conditions and changes in surface wind directions. Our results confirm that changes towards a predominace of north/northeasterly winds occured at these time intervals.
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