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Candidate Sites (candidate + site)
Selected AbstractsMolecular approaches to examine the phosphorylation state of the C type natriuretic peptide receptorJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2010Abdel A. Alli Abstract The intracellular domain of the C type natriuretic peptide receptor (NPRC) contains one threonine and several serine residues where phosphorylation is thought to occur. Several phosphorylation consensus sequences for various kinases have been identified within the intracellular domain of NPRC, but the exact residues that are phosphorylated and the specific kinases responsible for their phosphorylation have not been thoroughly defined. Here we introduce a recombinant GST fusion protein and a rat gastric mucosa (RGM1) cell line as molecular tools to study the phosphorylation state of NPRC in vitro and in vivo, respectively. We utilize a previously characterized polyclonal antibody against NPRC to probe for total NPRC protein and various phosphospecific and substrate motif antibodies to probe for phosphorylation of NPRC. Phosphoprotein staining reagents were used with a phosphoprotein control set to detect phosphorylation of NPRC at serine and threonine residues. Recombinant GST-NPRC fusion protein was phosphorylated in vitro by RGM1 lysate in the presence of adenosine-5'-triphosphate (ATP). Western blot analysis using a monoclonal phospho-Thr antibody, which exclusively detects phosphorylated threonine residues, and does not cross-react with phosphorylated serine residues revealed NPRC immunoprecipitated from RGM1 lysate is phosphorylated on a threonine residue. Global analysis of the entire rat NPRC sequence using a protein kinase A (PKA) prediction algorithm, identified five putative PKA phosphorylation sites containing a serine residue and one containing a threonine residue, Thr 505. Taken together, the data presented here suggest that rat NPRC is a substrate for PKA and Thr 505 located within the intracellular domain of NPRC is a likely candidate site for the phosphorylation. J. Cell. Biochem. 110: 985,994, 2010. © 2010 Wiley-Liss, Inc. [source] The effect of candidate familiarity on examiner OSCE scoresMEDICAL EDUCATION, Issue 9 2007Ann Jefferies Context, Although examiners are a large source of variability in the objective structured clinical examination (OSCE), the exact causes of examiner variance remain understudied. Objective, This study aimed to determine whether examiner familiarity with candidates influences candidate scores. Methods, A total of 24 candidates from 4 neonatal-perinatal training programmes participated in a 10-station OSCE. Sixteen trainees and 7 examiners came from a single centre (site A) and 8 candidates and 5 examiners came from the other 3 centres. Examiners completed station-specific binary checklists and an overall global rating; standardised patients (SPs) and standardised health professionals (SHPs) completed 4 process ratings and the overall rating. A fixed-effect, 2-way analysis of variance was performed to ascertain whether there was interaction between examiner site and candidate site. Results, Interstation Cronbach's , was 0.80 for the examiner checklist, 0.88 for the examiner global rating and 0.88 for the SP or SHP global rating. Although the checklist scores awarded by site A examiners were significantly higher than those awarded by non-site A examiners, there was no significant interaction between examiner and candidate site (P = 0.124). Similarly, the interaction between examiner and candidate site for the global rating was not significant (P = 0.207). Global ratings awarded by SPs and SHPs were also higher in stations where site A faculty examined site A candidates, suggesting the observed differences may have been related to performance. Conclusions, Results from this small dataset suggest that examiner familiarity with candidates does not influence how examiners score candidates, confirming the objective nature of the OSCE. Confirmation with a larger study is required. [source] Metropolitan Open-Space Protection with Uncertain Site AvailabilityCONSERVATION BIOLOGY, Issue 2 2005ROBERT G. HAIGHT acceso público; Chicago; modelo de selección de sitio; optimización; representación de especies Abstract:,Urban planners acquire open space to protect natural areas and provide public access to recreation opportunities. Because of limited budgets and dynamic land markets, acquisitions take place sequentially depending on available funds and sites. To address these planning features, we formulated a two-period site selection model with two objectives: maximize the expected number of species represented in protected sites and maximize the expected number of people with access to protected sites. These objectives were both maximized subject to an upper bound on area protected over two periods. The trade-off between species representation and public access was generated by the weighting method of multiobjective programming. Uncertainty was represented with a set of probabilistic scenarios of site availability in a linear-integer formulation. We used data for 27 rare species in 31 candidate sites in western Lake County, near the city of Chicago, to illustrate the model. Each trade-off curve had a concave shape in which species representation dropped at an increasing rate as public accessibility increased, with the trade-off being smaller at higher levels of the area budget. Several sites were included in optimal solutions regardless of objective function weights, and these core sites had high species richness and public access per unit area. The area protected in period one depended on current site availability and on the probabilities of sites being undeveloped and available in the second period. Although the numerical results are specific for our study, the methodology is general and applicable elsewhere. Resumen:,Planificadores urbanos adquieren espacios abiertos para proteger áreas naturales y proporcionar acceso público a oportunidades de recreación. Debido a presupuestos limitados y a la dinámica de los mercados de terrenos, las adquisiciones se llevan a cabo secuencialmente en función de la disponibilidad de fondos y sitios. Para atender estas características de la planificación, formulamos un modelo de selección de sitios de dos períodos con dos objetivos: maximizar el número esperado de especies representado en sitios protegidos y maximizar el número esperado de personas con acceso a sitios protegidos. Ambos objetivos fueron maximizados con un límite superior en la superficie protegida en los dos períodos. El balance entre la representación de especies y el acceso público fue generado por el método de ponderación de programación de multiobjetivos. La incertidumbre fue representada con un conjunto de escenarios probabilísticos de la disponibilidad de sitios en una formulación lineal-integral. Para demostrar el modelo, utilizamos datos para 27 especies raras en 31 sitios potenciales en el oeste del Condado Lake, cerca de la ciudad de Chicago. Cada curva tenía forma cóncava y la representación de especies descendió a medida que incrementó la accesibilidad pública, con un menor equilibrio en niveles altos del presupuesto para el área. Varios sitios fueron incluidos en soluciones óptimas independientemente de las funciones de ponderación de los objetivos, y estos sitios tuvieron alta riqueza de especies y acceso público por unidad de área. La superficie protegida en el período uno dependió de la disponibilidad de sitios y de las probabilidades de que los sitios no fueran desarrollados y de su disponibilidad en el segundo período. Aunque los resultados numéricos son específicos a nuestro estudio, la metodología es general y aplicable en otros sitios. [source] Dispersion of Nodes Added to a NetworkGEOGRAPHICAL ANALYSIS, Issue 4 2005Michael Kuby For location problems in which optimal locations can be at nodes or along arcs but no finite dominating set has been identified, researchers may desire a method for dispersing p additional discrete candidate sites along the m arcs of a network. This article develops and tests minimax and maximin models for solving this continuous network location problem, which we call the added-node dispersion problem (ANDP). Adding nodes to an arc subdivides it into subarcs. The minimax model minimizes the maximum subarc length, while the maximin model maximizes the minimum subarc length. Like most worst-case objectives, the minimax and maximin objectives are plagued by poorly behaved alternate optima. Therefore, a secondary MinSumMax objective is used to select the best-dispersed alternate optima. We prove that equal spacing of added nodes along arcs is optimal to the MinSumMax objective. Using this fact we develop greedy heuristic algorithms that are simple, optimal, and efficient (O(mp)). Empirical results show how the maximum subarc, minimum subarc, and sum of longest subarcs change as the number of added nodes increases. Further empirical results show how using the ANDP to locate additional nodes can improve the solutions of another location problem. Using the p-dispersion problem as a case study, we show how much adding ANDP sites to the network vertices improves the p-dispersion objective function compared with (a) network vertices only and (b) vertices plus randomly added nodes. The ANDP can also be used by itself to disperse facilities such as stores, refueling stations, cell phone towers, or relay facilities along the arcs of a network, assuming that such facilities already exist at all nodes of the network. [source] Contiguity Constraints for Single-Region Site Search ProblemsGEOGRAPHICAL ANALYSIS, Issue 4 2000Thomas J. Cova This paper proposes an explicit set of constraints as a general approach to the contiguity problem in site search modeling. Site search models address the challenging problem of identifying the best area in a study region for a particular land use, given that there are no candidate sites. Criteria that commonly arise in a search include a site's area, suitability, cost, shape, and proximity to surrounding geographic features. An unsolved problem in this modeling arena is the identification of a general set of mathematical programming constraints that can guarantee a contiguous solution (site) for any 0,1 integer-programming site search formulation. The constraints proposed herein address this problem, and we evaluate their efficacy and efficiency in the context of a regular and irregular tessellation of geographic space. An especially efficient constraint form is derived from a more general form and similarly evaluated. The results demonstrate that the proposed constraints represent a viable, general approach to the contiguity problem. [source] Regulation of the Murine TRACP Gene PromoterJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2003AI Cassady Abstract The activity of the TRACP promoter has been investigated as a model of gene regulation in osteoclasts. The murine TRACP gene promoter contains potential binding sites for a number of transcription factors in particular, candidate sites for the Ets factor PU.1 and for the microphthalmia transcription factor (MiTF). These are of relevance to osteoclast biology because the PU.1 knockout mouse has an osteopetrotic phenotype, and MiTF, when mutated in the mi/mi mouse, also results in osteopetrosis. The binding sites for both of these factors have been identified, and they have been determined to be functional in regulating TRACP expression. A novel assay system using the highly osteoclastogenic RAW/C4 subclone of the murine macrophage cell line RAW264.7 was used to perform gene expression experiments on macrophage and osteoclast cell backgrounds. We have shown that TRACP expression is a target for regulation by the macrophage/osteoclast transcription factor PU.1 and the osteoclast commitment factor MiTF and that these factors act synergistically in regulating this promoter. This directly links two controlling factors of osteoclast differentiation to the expression of an effector of cell function. [source] A hierarchical Bayesian model for predicting the functional consequences of amino-acid polymorphismsJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 1 2005Claudio J. Verzilli Summary., Genetic polymorphisms in deoxyribonucleic acid coding regions may have a phenotypic effect on the carrier, e.g. by influencing susceptibility to disease. Detection of deleterious mutations via association studies is hampered by the large number of candidate sites; therefore methods are needed to narrow down the search to the most promising sites. For this, a possible approach is to use structural and sequence-based information of the encoded protein to predict whether a mutation at a particular site is likely to disrupt the functionality of the protein itself. We propose a hierarchical Bayesian multivariate adaptive regression spline (BMARS) model for supervised learning in this context and assess its predictive performance by using data from mutagenesis experiments on lac repressor and lysozyme proteins. In these experiments, about 12 amino-acid substitutions were performed at each native amino-acid position and the effect on protein functionality was assessed. The training data thus consist of repeated observations at each position, which the hierarchical framework is needed to account for. The model is trained on the lac repressor data and tested on the lysozyme mutations and vice versa. In particular, we show that the hierarchical BMARS model, by allowing for the clustered nature of the data, yields lower out-of-sample misclassification rates compared with both a BMARS and a frequen-tist MARS model, a support vector machine classifier and an optimally pruned classification tree. [source] Perimeter air monitoring for soil remediationREMEDIATION, Issue 4 2007Guy J. Graening Most environmental project managers are well versed in characterizing and remediating contaminants in soil and water media. When soil remediation activities are conducted at an environmental site, however, some project managers are faced with monitoring contaminants in the air medium for the first time. Remediation activities can disturb contaminants that are normally immobile in soil and transfer them to air. The resulting increase in airborne concentrations of contaminants, even if temporary, may be a health concern for individuals in neighboring residences or businesses. Perimeter air monitoring may be required by a regulatory agency to determine if unhealthy conditions are created and if work practices should be limited or modified. This article serves as a resource for project managers involved in perimeter air monitoring for soil remediation and provides a general summary of candidate sites, remediation activities that release contaminants, regulatory requirements, equipment and target contaminants, monitoring locations and schedule, analytical methods, and data interpretation. © 2007 Wiley Periodicals, Inc. [source] | |||||||||||||