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91.
92.
Matthew O. Jones John S. Kimball Eric E. Small Kristine M. Larson 《International journal of biometeorology》2014,58(6):1305-1315
The land surface phenology (LSP) start of season (SOS) metric signals the seasonal onset of vegetation activity, including canopy growth and associated increases in land-atmosphere water, energy and carbon (CO2) exchanges influencing weather and climate variability. The vegetation optical depth (VOD) parameter determined from satellite passive microwave remote sensing provides for global LSP monitoring that is sensitive to changes in vegetation canopy water content and biomass, and insensitive to atmosphere and solar illumination constraints. Direct field measures of canopy water content and biomass changes desired for LSP validation are generally lacking due to the prohibitive costs of maintaining regional monitoring networks. Alternatively, a normalized microwave reflectance index (NMRI) derived from GPS base station measurements is sensitive to daily vegetation water content changes and may provide for effective microwave LSP validation. We compared multiyear (2007–2011) NMRI and satellite VOD records at over 300 GPS sites in North America, and their derived SOS metrics for a subset of 24 homogenous land cover sites to investigate VOD and NMRI correspondence, and potential NMRI utility for LSP validation. Significant correlations (P?<?0.05) were found at 276 of 305 sites (90.5 %), with generally favorable correspondence in the resulting SOS metrics (r 2?=?0.73, P?<?0.001, RMSE = 36.8 days). This study is the first attempt to compare satellite microwave LSP metrics to a GPS network derived reflectance index and highlights both the utility and limitations of the NMRI data for LSP validation, including spatial scale discrepancies between local NMRI measurements and relatively coarse satellite VOD retrievals. 相似文献
93.
Stewart G. Gardner Kristine D. Johns Rebecca Tanner William R. McCleary 《Journal of bacteriology》2014,196(9):1741-1752
Robust growth in many bacteria is dependent upon proper regulation of the adaptive response to phosphate (Pi) limitation. This response enables cells to acquire Pi with high affinity and utilize alternate phosphorous sources. The molecular mechanisms of Pi signal transduction are not completely understood. PhoU, along with the high-affinity, Pi-specific ATP-binding cassette transporter PstSCAB and the two-component proteins PhoR and PhoB, is absolutely required for Pi signaling in Escherichia coli. Little is known about the role of PhoU and its function in regulation. We have demonstrated using bacterial two-hybrid analysis and confirmatory coelution experiments that PhoU interacts with PhoR through its PAS (Per-ARNT-Sim) domain and that it also interacts with PstB, the cytoplasmic component of the transporter. We have also shown that the soluble form of PhoU is a dimer that binds manganese and magnesium. Alteration of highly conserved residues in PhoU by site-directed mutagenesis shows that these sites play a role in binding metals. Analysis of these phoU mutants suggests that metal binding may be important for PhoU membrane interactions. Taken together, these results support the hypothesis that PhoU is involved in the formation of a signaling complex at the cytoplasmic membrane that responds to environmental Pi levels. 相似文献
94.
Pawel Nowak Derek C. Cole Ann Aulabaugh Jonathan Bard Rajiv Chopra Rebecca Cowling Kristi Y. Fan Baihua Hu Steve Jacobsen Minakshi Jani Guixan Jin Mei-Chu Lo Michael S. Malamas Eric S. Manas Rani Narasimhan Peter Reinhart Albert J. Robichaud Joseph R. Stock Joan Subrath Kristine Svenson John W. Ellingboe 《Bioorganic & medicinal chemistry letters》2010,20(2):632-635
8,8-Diphenyl-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-amine (1) was identified through HTS, as a weak (micromolar) inhibitor of BACE1. X-Ray crystallographic studies indicate the 2-aminoimidazole ring forms key H-bonding interactions with Asp32 and Asp228 in the catalytic site of BACE1. Lead optimization using structure-based focused libraries led to the identification of low nanomolar BACE1 inhibitors such as 20b with substituents which extend from the S1 to the S3 pocket. 相似文献
95.
Christopher M. Harris Anna M. Ericsson Maria A. Argiriadi Claude Barberis David W. Borhani Andrew Burchat David J. Calderwood George A. Cunha Richard W. Dixon Kristine E. Frank Eric F. Johnson Joanne Kamens Silvia Kwak Biqin Li Kelly D. Mullen Denise C. Perron Lu Wang Neil Wishart Xiaoyun Wu Xiaolei Zhang Robert V. Talanian 《Bioorganic & medicinal chemistry letters》2010,20(1):334-337
We describe structure-based optimization of a series of novel 2,4-diaminopyrimidine MK2 inhibitors. Co-crystal structures (see accompanying Letter) demonstrated a unique inhibitor binding mode. Resulting inhibitors had IC50 values as low as 19 nM and moderate selectivity against a kinase panel. Compounds 15, 31a, and 31b inhibit TNFα production in peripheral human monocytes. 相似文献
96.
97.
Sandra Lightle Serdar Aykent Nathan Lacher Vesselin Mitaksov Kristine Wells James Zobel Theodore Oliphant 《Protein science : a publication of the Protein Society》2010,19(4):753-762
Human IgG2 antibodies may exist in at least three distinct structural isomers due to disulfide shuffling within the upper hinge region. Antibody interactions with Fc gamma receptors and the complement component C1q contribute to immune effector functions. These interactions could be impacted by the accessibility and structure of the hinge region. To examine the role structural isomers may have on effector functions, a series of cysteine to serine mutations were made on a human IgG2 backbone. We observed structural homogeneity with these mutants and mapped the locations of their disulfide bonds. Importantly, there was no observed difference in binding to any of the Fc gamma receptors or C1q between the mutants and the wild‐type IgG2. However, differences were seen in the apparent binding affinity of these antibodies that were dependent on the selection of the secondary detection antibody used. 相似文献
98.
Kevin M. Waters Daniel O. Stram Mohamed T. Hassanein Lo?c Le Marchand Lynne R. Wilkens Gertraud Maskarinec Kristine R. Monroe Laurence N. Kolonel David Altshuler Brian E. Henderson Christopher A. Haiman 《PLoS genetics》2010,6(8)
It has been recently hypothesized that many of the signals detected in genome-wide association studies (GWAS) to T2D and other diseases, despite being observed to common variants, might in fact result from causal mutations that are rare. One prediction of this hypothesis is that the allelic associations should be population-specific, as the causal mutations arose after the migrations that established different populations around the world. We selected 19 common variants found to be reproducibly associated to T2D risk in European populations and studied them in a large multiethnic case-control study (6,142 cases and 7,403 controls) among men and women from 5 racial/ethnic groups (European Americans, African Americans, Latinos, Japanese Americans, and Native Hawaiians). In analysis pooled across ethnic groups, the allelic associations were in the same direction as the original report for all 19 variants, and 14 of the 19 were significantly associated with risk. In summing the number of risk alleles for each individual, the per-allele associations were highly statistically significant (P<10−4) and similar in all populations (odds ratios 1.09–1.12) except in Japanese Americans the estimated effect per allele was larger than in the other populations (1.20; Phet = 3.8×10−4). We did not observe ethnic differences in the distribution of risk that would explain the increased prevalence of type 2 diabetes in these groups as compared to European Americans. The consistency of allelic associations in diverse racial/ethnic groups is not predicted under the hypothesis of Goldstein regarding “synthetic associations” of rare mutations in T2D. 相似文献
99.
Todd J. Brinkman Michael K. Schwartz David K. Person Kristine L. Pilgrim Kris J. Hundertmark 《Conservation Genetics》2010,11(4):1547-1552
Non-invasive wildlife research using DNA from feces has become increasingly popular. Recent studies have attempted to solve
problems associated with recovering DNA from feces by investigating the influence of factors such as season, diet, collection
method, preservation method, extraction protocol, and time. To our knowledge, studies of this nature have not addressed DNA
degradation over time in wet environments, and have not been performed on fecal pellets of ungulates. Therefore, our objective
was to determine the length of time a fecal pellet from a Sitka black-tailed deer (Odocoileus hemionus sitkensis) could remain in the field in a temperate rainforest environment before the DNA became too degraded for individual identification.
Pellets were extracted from the rectum of recently killed deer and placed in an environment protected from rainfall and in
an environment exposed to rainfall. Pellets from each treatment group were sampled at intervals of 2, 7, 14, 21, and 28 days
after deer harvest. DNA was extracted from sampled pellets and individual samples were genotyped using microsatellite markers.
Amplification failure and errors (dropout and false alleles) were recorded to determine extent of DNA degradation. Eighty
percent of samples in the protected environment and 22% of samples in the exposed environment were successfully genotyped
during the 28-day experiment. With no samples being successfully genotyped in the exposed environment after 7 days, our study
showed that rainfall significantly increases degradation rates of DNA from ungulate pellets. 相似文献
100.