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    ๋…ผ์˜๋ฅผ ๊ฐ•์กฐํ•œ ํƒ๊ตฌ ํ•™์Šต๋ฒ•์— ๋”ฐ๋ฅธ ์ดˆ๋“ฑํ•™๊ต ํ†ตํ•ฉํ•™์ƒ์˜ ๊ณผํ•™๊ณผ ์ˆ˜ํ•™ ํ•™์—…์„ฑ์ทจ๋„ ๋ฐ ๋น„ํŒ์  ์‚ฌ๊ณ ๋ ฅ๊ณผ์˜ ๊ด€๊ณ„ ๋ถ„์„

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    ๋ณธ ์—ฐ๊ตฌ์˜ ๋ชฉ์ ์€ ๋…ผ์˜๋ฅผ ๊ฐ•์กฐํ•œ ํƒ๊ตฌ ํ•™์Šต๋ฒ•์ด ํŠน๋ณ„ํ•œ ๊ต์œก์  ์ง€์›์ด ํ•„์š”ํ•œ ์ดˆ๋“ฑํ•™๊ต ํ†ตํ•ฉํ•™์ƒ๋“ค์˜ ๊ณผํ•™ ๋ฐ ์ˆ˜ํ•™ ๋Šฅ๋ ฅ์— ๋ฏธ์น˜๋Š” ๋ฐ ์žˆ๋‹ค. ์ด ์—ฐ๊ตฌ์˜ ๋ชฉ์ ์„ ์œ„ํ•ด์„œ ๋ฏธ๊ตญ ์ค‘๋ถ€์˜ ํ•œ ์ฃผ(state)์˜ 48๊ฐœ ์ผ๋ฐ˜ ์ดˆ๋“ฑํ•™๊ต๋ฅผ ํƒ๊ตฌ์  ๊ณผํ•™ ๊ธ€์“ฐ๊ธฐ ํ™œ๋™์„ ์‹ค์‹œํ•œ 24๊ฐœ์˜ ์‹คํ—˜์ง‘๋‹จ ํ•™๊ต์™€, ์ด ์ค‘์žฌํ•™์Šต์„ ์‹ค์‹œํ•˜์ง€ ์•Š์€ 24๊ฐœ์˜ ๋น„๊ต์ง‘๋‹จ ํ•™๊ต๋กœ ๋‚˜๋ˆ„์–ด, ๊ฐ ํ•™๊ต์—์„œ ํ†ตํ•ฉ๊ต์œก ์„ ๋ฐ›๊ณ  ์žˆ๋Š” ํ•™์ƒ๋“ค์„ ๋Œ€์ƒ์œผ๋กœ ๋น„ํŒ์  ์‚ฌ๊ณ ๋ ฅ ๊ฒ€์‚ฌ์™€ ๊ณผํ•™ ๋ฐ ์ˆ˜ํ•™๋Šฅ๋ ฅ ์˜ํ–ฅ์„ ์•Œ์•„๋ณด๊ณ , ํ•™์ƒ๋“ค์˜ ๋น„ํŒ์  ์‚ฌ๊ณ ๋ ฅ๊ณผ ๊ณผํ•™ ๋ฐ ์ˆ˜ํ•™ ๊ต๊ณผ ๋Šฅ๋ ฅ ๊ฐ„์˜ ๊ด€๊ณ„๋ฅผ ๋ถ„์„ํ•˜๋Š” ๊ฒ€์‚ฌ๋ฅผ ์‹ค์‹œํ•˜์˜€๋‹ค. ๋‘ ์ง‘๋‹จ ๊ฐ„์— ๋น„ํŒ์  ์‚ฌ๊ณ ๋ ฅ์˜ 4๊ฐœ ํ•˜์œ„๋ฒ”์ฃผ์ธ ๊ท€๋‚ฉ์  ์‚ฌ๊ณ ๋ ฅ, ์—ฐ์—ญ์  ์‚ฌ๊ณ ๋ ฅ, ๊ด€์ฐฐ์  ์‚ฌ๊ณ  ๋ ฅ, ์ถ”์ •์  ์‚ฌ๊ณ ๋ ฅ ๊ฒ€์‚ฌ๊ฒฐ๊ณผ๋ฅผ ๋น„๊ตํ•˜์˜€๊ณ , ๋น„ํŒ์  ์‚ฌ๊ณ ๋ ฅ๊ณผ ๊ณผํ•™ ๋ฐ ์ˆ˜ํ•™ ํ•™์—… ์„ฑ์ทจ๋„ ๊ฐ„์˜ ์ƒ๊ด€๊ด€๊ณ„ ๋ถ„์„ ๋ฐ ํšŒ๊ท€ ๋ถ„์„์„ ์‹ค์‹œํ•˜์˜€๋‹ค. ์—ฐ๊ตฌ ๊ฒฐ๊ณผ, ๋…ผ์˜๋ฅผ ๊ฐ•์กฐํ•œ ํƒ๊ตฌ ํ•™์Šต๋ฒ•์„ ๊ฒฝํ—˜ํ•œ ํ•™์ƒ๋“ค์ด 1๋…„๊ฐ„์˜ ์ค‘์žฌ๋ฅผ ํ†ตํ•ด์„œ ๊ณผํ•™ ๋Šฅ๋ ฅ ๋ฐ ์ˆ˜ํ•™๋Šฅ๋ ฅ์ด ์ฆ๊ฐ€ํ•˜์˜€๋‹ค. ํ•™์ƒ๋“ค์˜ ๋น„ํŒ์  ์‚ฌ ๊ณ ๋ ฅ์— ์žˆ์–ด์„œ๋Š”, ๊ตฌ์ฒด์ ์œผ๋กœ ๊ท€๋‚ฉ์  ์‚ฌ๊ณ ๋ ฅ, ์—ฐ์—ญ์  ์‚ฌ๊ณ ๋ ฅ, ๊ด€์ฐฐ์  ์‚ฌ๊ณ ๋ ฅ์€ ํ•™์ƒ๋“ค์˜ ๊ณผ ํ•™ ๋ฐ ์ˆ˜ํ•™๋Šฅ๋ ฅ๊ณผ ์œ ์˜๋ฏธํ•œ ์ƒ๊ด€๊ด€๊ณ„๋ฅผ ๋ณด์˜€๊ณ , ํšŒ๊ท€๋ถ„์„์„ ํ†ตํ•ด์„œ๋„ ํ•™์ƒ๋“ค์˜ ๊ท€๋‚ฉ์  ์‚ฌ๊ณ  ๋ ฅ๊ณผ ๊ด€์ฐฐ์  ์‚ฌ๊ณ ๋ ฅ์„ ํ†ตํ•˜์—ฌ ๊ณผํ•™ ๋ฐ ์ˆ˜ํ•™๋Šฅ๋ ฅ ํ–ฅ์ƒ์„ ์„ค๋ช…ํ•  ์ˆ˜ ์žˆ๋Š” ํšŒ๊ท€ ๋ชจํ˜•์„ ๋ฐœ๊ฒฌํ•˜ ์˜€๋‹ค. ์ด๋Ÿฌํ•œ ๊ฒฐ๊ณผ๋ฅผ ํ†ตํ•ด ๋ณผ ๋•Œ, ํŠน๋ณ„ํ•œ ๊ต์œก์  ์ง€์› ์š”๊ตฌ๋ฅผ ๊ฐ€์ง„ ํ•™์ƒ๋“ค์˜ ๊ณผํ•™ ๋ฐ ์ˆ˜ํ•™๋Šฅ ๋ ฅ ํ–ฅ์ƒ์„ ์œ„ํ•ด์„œ๋Š”, ํ•™์ƒ๋“ค๋กœ ํ•˜์—ฌ๊ธˆ ์ข€ ๋” ๊ตฌ์ฒด์ ์ธ ๊ฒฝํ—˜ ๋ฐ ์ง์ ‘์ ์ธ ๊ด€์ฐฐ์„ ํ†ตํ•ด์„œ ํ•™์Šต ์„ ํ•  ์ˆ˜ ์žˆ๋„๋ก ํ•˜๋Š” ๊ฒƒ์ด ์ค‘์š”ํ•˜๋‹ค๊ณ  ํ•  ์ˆ˜ ์žˆ๊ฒ ๋‹ค. ํ•˜์ง€๋งŒ ๋น„ํŒ์  ์‚ฌ๊ณ ๋ ฅ์˜ ํ•œ ์˜์—ญ์ธ ์ถ” ์ •์  ์‚ฌ๊ณ ๋ ฅ์€ ํŠน๋ณ„ํ•œ ๊ต์œก์  ์ง€์›์š”๊ตฌ๋ฅผ ์ง€๋‹Œ ์ดˆ๋“ฑํ•™๊ต ํ†ตํ•ฉํ•™์ƒ๋“ค์˜ ๊ณผํ•™ ๋ฐ ์ˆ˜ํ•™๋Šฅ๋ ฅ ํ–ฅ ์ƒ๊ณผ ๊ด€๊ณ„๊ฐ€ ์—†๋Š” ๊ฒƒ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ๊ทธ๋Ÿผ์—๋„ ๋ถˆ๊ตฌํ•˜๊ณ  ๋น„ํŒ์  ์‚ฌ๊ณ ๋ ฅ์˜ ํ•ต์‹ฌ์š”์†Œ๋ผ ํ•  ์ˆ˜ ์žˆ๋Š” ์ถ”์ •์  ์‚ฌ๊ณ ๋ ฅ์„ ํ–ฅ์ƒ์‹œํ‚ค๋Š” ๊ฒƒ์ด ์™œ ์ค‘์š”ํ•œ์ง€, ํ›„์† ์—ฐ๊ตฌ๋ฅผ ํ†ตํ•ด์„œ ์ด๋ฅผ ํ–ฅ์ƒ์‹œํ‚ฌ ์ˆ˜ ์žˆ ๋Š” ์ค‘์žฌ๋ฐฉ๋ฒ•์„ ์ƒˆ๋กญ๊ฒŒ ๊ณ ์•ˆํ•ด์•ผ ํ•˜๋Š” ์ด์œ ์— ๋Œ€ํ•ด์„œ ๋…ผ์˜๋ฅผ ํ†ตํ•˜์—ฌ ์ œ์‹œํ•˜์˜€๋‹ค

    Phenotype and Function of CD209+ Bovine Blood Dendritic Cells, Monocyte-Derived- Dendritic Cells and Monocyte-Derived Macrophages

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    Phylogenic comparisons of the mononuclear phagocyte system (MPS) of humans and mice demonstrate phenotypic divergence of dendritic cell (DC) subsets that play similar roles in innate and adaptive immunity. Although differing in phenotype, DC can be classified into four groups according to ontogeny and function: conventional DC (cDC1 and cDC2), plasmacytoid DC (pDC), and monocyte derived DC (MoDC). DC of Artiodactyla (pigs and ruminants) can also be sub-classified using this system, allowing direct functional and phenotypic comparison of MoDC and other DC subsets trafficking in blood (bDC). Because of the high volume of blood collections required to study DC, cattle offer the best opportunity to further our understanding of bDC and MoDC function in an outbred large animal species. As reported here, phenotyping DC using a monoclonal antibody (mAb) to CD209 revealed CD209 is expressed on the major myeloid population of DC present in blood and MoDC, providing a phenotypic link between these two subsets. Additionally, the present study demonstrates that CD209 is also expressed on monocyte derived macrophages (Moฮฆ). Functional analysis revealed each of these populations can take up and process antigens (Ags), present them to CD4 and CD8 T cells, and elicit a T-cell recall response. Thus, bDC, MoDC, and Moฮฆ pulsed with pathogens or candidate vaccine antigens can be used to study factors that modulate DC-driven T-cell priming and differentiation ex vivo

    Phenotype and Function of CD209+ Bovine Blood Dendritic Cells, Monocyte-Derived- Dendritic Cells and Monocyte-Derived Macrophages

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    Phylogenic comparisons of the mononuclear phagocyte system (MPS) of humans and mice demonstrate phenotypic divergence of dendritic cell (DC) subsets that play similar roles in innate and adaptive immunity. Although differing in phenotype, DC can be classified into four groups according to ontogeny and function: conventional DC (cDC1 and cDC2), plasmacytoid DC (pDC), and monocyte derived DC (MoDC). DC of Artiodactyla (pigs and ruminants) can also be sub-classified using this system, allowing direct functional and phenotypic comparison of MoDC and other DC subsets trafficking in blood (bDC). Because of the high volume of blood collections required to study DC, cattle offer the best opportunity to further our understanding of bDC and MoDC function in an outbred large animal species. As reported here, phenotyping DC using a monoclonal antibody (mAb) to CD209 revealed CD209 is expressed on the major myeloid population of DC present in blood and MoDC, providing a phenotypic link between these two subsets. Additionally, the present study demonstrates that CD209 is also expressed on monocyte derived macrophages (Moฮฆ). Functional analysis revealed each of these populations can take up and process antigens (Ags), present them to CD4 and CD8 T cells, and elicit a T-cell recall response. Thus, bDC, MoDC, and Moฮฆ pulsed with pathogens or candidate vaccine antigens can be used to study factors that modulate DC-driven T-cell priming and differentiation ex vivo

    Temporal pattern of C1q deposition after transient focal cerebral ischemia

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    Recent studies have focused on elucidating the contribution of individual complement proteins to post-ischemic cellular injury. As the timing of complement activation and deposition after cerebral ischemia is not well understood, our study investigates the temporal pattern of C1q accumulation after experimental murine stroke. Brains were harvested from mice subjected to transient focal cerebral ischemia at 3, 6, 12, and 24 hr post reperfusion. Western blotting and light microscopy were employed to determine the temporal course of C1q protein accumulation and correlate this sequence with infarct evolution observed with TTC staining. Confocal microscopy was utilized to further characterize the cellular localization and characteristics of C1q deposition. Western Blot analysis showed that C1q protein begins to accumulate in the ischemic hemisphere between 3 and 6 hr post-ischemia. Light microscopy confirmed these findings, showing concurrent C1q protein staining of neurons. Confocal microscopy demonstrated co-localization of C1q protein with neuronal cell bodies as well as necrotic cellular debris. These experiments demonstrate the accumulation of C1q protein on neurons during the period of greatest infarct evolution. This data provides information regarding the optimal time window during which a potentially neuroprotective anti-C1q strategy is most likely to achieve therapeutic success. ยฉ 2006 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50651/1/20775_ftp.pd

    3C236: Radio Source, Interrupted?

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    We present new HST STIS/MAMA near-UV images and archival WFPC2 V and R band images which reveal the presence of four star forming regions in an arc along the edge of the dust lane in the giant (4 Mpc) radio galaxy 3C236. Two of the star forming regions are relatively young with ages of order 1E7 yr, while the other two are older with ages of order 1E8 - 1E9 yr which is comparable to the estimated age of the giant radio source. Based on dynamical and spectral aging arguments, we suggest that the fuel supply to the AGN was interrupted for 1E7 yr and has now been restored, resulting in the formation of the inner 2 kpc scale radio source. This time scale is similar to that of the age of the youngest of the star forming regions. We suggest that the transport of gas in the disk is non-steady and that this produces both the multiple episodes of star formation in the disk as well as the multiple epochs of radio source activity. If the inner radio source and the youngest star forming region are related by the same event of gas transport, the gas must be transported from the hundreds of pc scale to the sub-parsec scale on a time scale of 1E7 yr, which is similar to the dynamical time scale of the gas on the hundreds of pc scales

    Arctic tundra shrubification: a review of mechanisms and impacts on ecosystem carbon balance

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    Vegetation composition shifts, and in particular, shrub expansion across the Arctic tundra are some of the most important and widely observed responses of high-latitude ecosystems to rapid climate warming. These changes in vegetation potentially alter ecosystem carbon balances by affecting a complex set of soil-plant-atmosphere interactions. In this review, we synthesize the literature on (a) observed shrub expansion, (b) key climatic and environmental controls and mechanisms that affect shrub expansion, (c) impacts of shrub expansion on ecosystem carbon balance, and (d) research gaps and future directions to improve process representations in land models. A broad range of evidence, including in-situ observations, warming experiments, and remotely sensed vegetation indices have shown increases in growth and abundance of woody plants, particularly tall deciduous shrubs, and advancing shrublines across the circumpolar Arctic. This recent shrub expansion is affected by several interacting factors including climate warming, accelerated nutrient cycling, changing disturbance regimes, and local variation in topography and hydrology. Under warmer conditions, tall deciduous shrubs can be more competitive than other plant functional types in tundra ecosystems because of their taller maximum canopy heights and often dense canopy structure. Competitive abilities of tall deciduous shrubs vs herbaceous plants are also controlled by variation in traits that affect carbon and nutrient investments and retention strategies in leaves, stems, and roots. Overall, shrub expansion may affect tundra carbon balances by enhancing ecosystem carbon uptake and altering ecosystem respiration, and through complex feedback mechanisms that affect snowpack dynamics, permafrost degradation, surface energy balance, and litter inputs. Observed and projected tall deciduous shrub expansion and the subsequent effects on surface energy and carbon balances may alter feedbacks to the climate system. Land models, including those integrated in Earth System Models, need to account for differences in plant traits that control competitive interactions to accurately predict decadal- to centennial-scale tundra vegetation and carbon dynamics

    Comparative Effectiveness of Oxaliplatin Versus 5-flourouricil in Older Adults: An Instrumental Variable Analysis

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    Oxaliplatin was rapidly adopted for treatment of stage III colon cancer after FDA approval in November 2004, thus providing an opportunity to use calendar time as an instrumental variable (IV) in nonexperimental comparative effectiveness research. Assuming instrument validity, IV analyses account for unmeasured confounding and are particularly valuable in sub-populations of unresolved effectiveness such as older individuals

    The Dawn of Open Access to Phylogenetic Data

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    The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

    A universal probe set for targeted sequencing of 353 nuclear genes from any flowering plant designed using k-medoids clustering

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    Sequencing of target-enriched libraries is an efficient and cost-effective method for obtaining DNA sequenceย data from hundreds of nuclear loci for phylogeny reconstruction. Much of the cost of developing targeted sequencingย approaches is associated with the generation of preliminary data needed for the identification of orthologous loci for probeย design. In plants, identifying orthologous loci has proven difficult due to a large number of whole-genome duplicationย events, especially in the angiosperms (flowering plants).We used multiple sequence alignments from over 600 angiospermsย for 353 putatively single-copy protein-coding genes identified by the One Thousand Plant Transcriptomes Initiative toย design a set of targeted sequencing probes for phylogenetic studies of any angiosperm group. To maximize the phylogeneticย potential of the probes, while minimizing the cost of production, we introduce a k-medoids clustering approach to identifyย the minimum number of sequences necessary to represent each coding sequence in the final probe set. Using this method,ย 5โ€“15 representative sequences were selected per orthologous locus, representing the sequence diversity of angiospermsย more efficiently than if probes were designed using available sequenced genomes alone. To test our approximately 80,000ย probes, we hybridized libraries from 42 species spanning all higher-order groups of angiosperms, with a focus on taxa notย present in the sequence alignments used to design the probes. Out of a possible 353 coding sequences, we recovered anย average of 283 per species and at least 100 in all species. Differences among taxa in sequence recovery could not be explainedย by relatedness to the representative taxa selected for probe design, suggesting that there is no phylogenetic bias in theย probe set. Our probe set, which targeted 260 kbp of coding sequence, achieved a median recovery of 137 kbp per taxon inย coding regions, a maximum recovery of 250 kbp, and an additional median of 212 kbp per taxon in flanking non-codingย regions across all species. These results suggest that the Angiosperms353 probe set described here is effective for any groupย of flowering plants and would be useful for phylogenetic studies from the species level to higher-order groups, including the entire angiosperm clade itself

    Scaffold-mediated Nucleation of Protein Signaling Complexes: Elementary Principles

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    Proteins with multiple binding sites play important roles in cell signaling systems by nucleating protein complexes in which, for example, enzymes and substrates are co-localized. Proteins that specialize in this function are called by a variety names, including adapter, linker and scaffold. Scaffold-mediated nucleation of protein complexes can be either constitutive or induced. Induced nucleation is commonly mediated by a docking site on a scaffold that is activated by phosphorylation. Here, by considering minimalist mathematical models, which recapitulate scaffold effects seen in more mechanistically detailed models, we obtain analytical and numerical results that provide insights into scaffold function. These results elucidate how recruitment of a pair of ligands to a scaffold depends on the concentrations of the ligands, on the binding constants for ligand-scaffold interactions, on binding cooperativity, and on the milieu of the scaffold, as ligand recruitment is affected by competitive ligands and decoy receptors. For the case of a bivalent scaffold, we obtain an expression for the unique scaffold concentration that maximally recruits a pair of monovalent ligands. Through simulations, we demonstrate that a bivalent scaffold can nucleate distinct sets of ligands to equivalent extents when the scaffold is present at different concentrations. Thus, the function of a scaffold can potentially change qualitatively with a change in copy number. We also demonstrate how a scaffold can change the catalytic efficiency of an enzyme and the sensitivity of the rate of reaction to substrate concentration. The results presented here should be useful for understanding scaffold function and for engineering scaffolds to have desired properties.Comment: 12 pages, 8 figure
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