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21.
Raboisson P de Kock H Rosenquist A Nilsson M Salvador-Oden L Lin TI Roue N Ivanov V Wähling H Wickström K Hamelink E Edlund M Vrang L Vendeville S Van de Vreken W McGowan D Tahri A Hu L Boutton C Lenz O Delouvroy F Pille G Surleraux D Wigerinck P Samuelsson B Simmen K 《Bioorganic & medicinal chemistry letters》2008,18(17):4853-4858
SAR analysis performed with a limited set of cyclopentane-containing macrocycles led to the identification of N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (Ki = 0.36 nM) and viral replication (replicon EC50 = 7.8 nM). TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. TMC435350 is currently being evaluated in the clinics. 相似文献
22.
δ13C values of C3 plants are indicators of plant carbon–water relations that integrate plant responses to environmental conditions. However,
few studies have quantified spatial variation in plant δ13C at the landscape scale. We determined variation in leaf δ13C, leaf nitrogen per leaf area (Narea), and specific leaf area (SLA) in April and August 2005 for all individuals of three common woody species within a 308 × 12-m
belt transect spanning an upland–lowland topoedaphic gradient in a subtropical savanna in southern Texas. Clay content, available
soil moisture, and soil total N were all negatively correlated with elevation. The δ13C values of Prosopis glandulosa (deciduous N2-fixing tree legume), Condalia hookeri (evergreen shrub), and Zanthoxylum fagara (evergreen shrub) leaves increased 1–4‰ with decreasing elevation, with the δ13C value of P. glandulosa leaves being 1–3‰ higher than those of the two shrub species. Contrary to theory and results from previous studies, δ13C values were highest where soil water was most available, suggesting that some other variable was overriding or interacting
with water availability. Leaf Narea was positively correlated with leaf δ13C of all species (p < 0.01) and appeared to exert the strongest control over δ13C along this topoedaphic gradient. Since leaf Narea is positively related to photosynthetic capacity, plants with high leaf Narea are likely to have low p
I/p
a ratios and therefore higher δ13C values, assuming stomatal conductance is constant. Specific leaf area was not correlated significantly with leaf δ13C. Following a progressive growing season drought in July/August, leaf δ13C decreased. The lower δ13C in August may reflect the accumulation of 13C-depleted epicuticular leaf wax. We suggest control of leaf δ13C along this topoedaphic gradient is mediated by leaf Narea rather than by stomatal conductance limitations associated with water availability. 相似文献
23.
The spatial distribution of soil organic carbon in tidal wetland soils of the continental United States
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Audra L. Hinson Rusty A. Feagin Marian Eriksson Raymond G. Najjar Maria Herrmann Thomas S. Bianchi Michael Kemp Jack A. Hutchings Steve Crooks Thomas Boutton 《Global Change Biology》2017,23(12):5468-5480
Tidal wetlands contain large reservoirs of carbon in their soils and can sequester carbon dioxide (CO2) at a greater rate per unit area than nearly any other ecosystem. The spatial distribution of this carbon influences climate and wetland policy. To assist with international accords such as the Paris Climate Agreement, national‐level assessments such as the United States (U.S.) National Greenhouse Gas Inventory, and regional, state, local, and project‐level evaluation of CO2 sequestration credits, we developed a geodatabase (CoBluCarb) and high‐resolution maps of soil organic carbon (SOC) distribution by linking National Wetlands Inventory data with the U.S. Soil Survey Geographic Database. For over 600,000 wetlands, the total carbon stock and organic carbon density was calculated at 5‐cm vertical resolution from 0 to 300 cm of depth. Across the continental United States, there are 1,153–1,359 Tg of SOC in the upper 0–100 cm of soils across a total of 24 945.9 km2 of tidal wetland area, twice as much carbon as the most recent national estimate. Approximately 75% of this carbon was found in estuarine emergent wetlands with freshwater tidal wetlands holding about 19%. The greatest pool of SOC was found within the Atchafalaya/Vermilion Bay complex in Louisiana, containing about 10% of the U.S. total. The average density across all tidal wetlands was 0.071 g cm?3 across 0–15 cm, 0.055 g cm?3 across 0–100 cm, and 0.040 g cm?3 at the 100 cm depth. There is inherent variability between and within individual wetlands; however, we conclude that it is possible to use standardized values at a range of 0–100 cm of the soil profile, to provide first‐order quantification and to evaluate future changes in carbon stocks in response to environmental perturbations. This Tier 2‐oriented carbon stock assessment provides a scientific method that can be copied by other nations in support of international requirements. 相似文献
24.
25.
Annette AM Gerritsen Rob JPM Scholten Willem JJ Assendelft Herman Kuiper Henrica CW de Vet Lex M Bouter 《BMC neurology》2001,1(1):8-7
Background
Carpal tunnel syndrome is a common disorder, which can be treated with surgery or conservative options. However, there is insufficient evidence and no consensus among physicians with regard to the preferred treatment for carpal tunnel syndrome. Therefore, a randomized controlled trial is conducted to compare the short- and long-term efficacy of surgery and splinting in patients with carpal tunnel syndrome. An attempt is also made to avoid the (methodological) limitations encountered in earlier trials on the efficacy of various treatment options for carpal tunnel syndrome. 相似文献26.
27.
Postsynaptic density antigens: preparation and characterization of an antiserum against postsynaptic densities 总被引:6,自引:3,他引:3
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Long-term immunization of rabbits with postsynaptic densities (PSD) from bovine brain produced an antiserum specific for PSD as judged by binding to subcellular fractions and immunohistochemical location at the light and electron microscope levels. (a) The major antigens of bovine PSD preparations were three polypeptides of molecular weight 95,000 (PSD-95), 82,000 (PSD-82), and 72,000 (PSD-72), respectively. Antigen PSD-95, also present in mouse and rat PSDs was virtually absent from cytoplasm, myelin, mitochondria, and microsomes from rodent or bovine brain. Antigens PSD-82 and PSD-72 were present in all subcellular fractions from bovine brain, especially in mitochondria, but were almost absent from rodent brain. The antiserum also contained low-affinity antibodies against tubulin. (b)Immunohistochemical studies were performed in mouse and rat brain, where antigen PSD-95 accounted for 90 percent of the antiserum binding after adsorption with purified brain tubulin. At the light microscope level, antibody binding was observed only in those regions of the brain where synapses are known to be present. No reaction was observed in myelinated tracts, in the neuronal cytoplasm, or in nonneuronal cells. Strong reactivity was observed in the molecular layer of the dentate gyrus, stratum oriens and stratum radiatum of the hippocampus, and the molecular layer of the cerebellum. Experimental lesions, such as ablation of the rat entorhinal cortex or intraventricular injection of kainic acid, which led to a major loss of PSD in well- defined areas of the hippocampal formation, caused a correlative decrease in immunoreactivity in these areas. Abnormal patterns of immunohistochemical staining correlated with abnormal synaptic patterns in the cerebella of reeler and staggerer mouse mutants. (c) At the electron microscopic level, immunoreactivity was detectable only in PSD. The antibody did not bind to myelin, mitochondria or plasma membranes. (d) The results indicate that antigen PSD-95 is located predominantly or exclusively in PSD and can be used as a marker during subcellular fractionation. Other potential uses include the study of synaptogenesis, and the detection of changes in synapse number after experimental perturbations of the nervous system. 相似文献
28.
Flendrie M Vissers WH Creemers MC de Jong EM van de Kerkhof PC van Riel PL 《Arthritis research & therapy》2005,7(3):R666-R676
Various dermatological conditions have been reported during tumor necrosis factor (TNF)-α-blocking therapy, but until now
no prospective studies have been focused on this aspect. The present study was set up to investigate the number and nature
of clinically important dermatological conditions during TNF-α-blocking therapy in patients with rheumatoid arthritis (RA).
RA patients starting on TNF-α-blocking therapy were prospectively followed up. The numbers and natures of dermatological events
giving rise to a dermatological consultation were recorded. The patients with a dermatological event were compared with a
group of prospectively followed up RA control patients, naive to TNF-α-blocking therapy and matched for follow-up period.
289 RA patients started TNF-α-blocking therapy. 128 dermatological events were recorded in 72 patients (25%) during 911 patient-years
of follow-up. TNF-α-blocking therapy was stopped in 19 (26%) of these 72 patients because of the dermatological event. More
of the RA patients given TNF-α-blocking therapy (25%) than of the anti-TNF-α-naive patients (13%) visited a dermatologist
during follow-up (P < 0.0005). Events were recorded more often during active treatment (0.16 events per patient-year) than during the period
of withdrawal of TNF-α-blocking therapy (0.09 events per patient-year, P < 0.0005). The events recorded most frequently were skin infections (n = 33), eczema (n = 20), and drug-related eruptions (n = 15). Other events with a possible relation to TNF-α-blocking therapy included vasculitis, psoriasis, drug-induced systemic
lupus erythematosus, dermatomyositis, and a lymphomatoid-papulosis-like eruption. This study is the first large prospective
study focusing on dermatological conditions during TNF-α-blocking therapy. It shows that dermatological conditions are a significant
and clinically important problem in RA patients receiving TNF-α-blocking therapy. 相似文献
29.
Peter Ghosh Jiehua Wu Susan Shimmon Andrew CW Zannettino Stan Gronthos Silviu Itescu 《Arthritis research & therapy》2010,12(1):R28
Introduction
This study was undertaken to determine whether the anti-osteoarthritis drug pentosan polysulfate (PPS) influenced mesenchymal precursor cell (MPC) proliferation and differentiation. 相似文献30.
Sabine JM de Brouwer Floris W Kraaimaat Fred CGJ Sweep Marjonne CW Creemers Timothy RDJ Radstake Antoinette IM van Laarhoven Piet LCM van Riel Andrea WM Evers 《Arthritis research & therapy》2010,12(3):R89