Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor

Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind related GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. The structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes.

On the Lp-Norm Regression Models for Estimating Value-at-Risk

Analysis of risk measures associated with price series data movements and its predictions are of strategic importance in the financial markets as well as to policy makers in particular for short- and longterm planning for setting up economic growth targets. For example, oilprice risk-management focuses primarily on when and how an organization can best prevent the costly exposure to price risk. Value-at-Risk (VaR) is the commonly practised instrument to measure risk and is evaluated by analysing the negative/positive tail of the probability distributions of the returns (profit or loss). In modelling applications, least-squares estimation (LSE)-based linear regression models are often employed for modeling and analyzing correlated data. These linear models are optimal and perform relatively well under conditions such as errors following normal or approximately normal distributions, being free of large size outliers and satisfying the Gauss-Markov assumptions. However, often in practical situations, the LSE-based linear regression models fail to provide optimal results, for instance, in non-Gaussian situations especially when the errors follow distributions with fat tails and error terms possess a finite variance. This is the situation in case of risk analysis which involves analyzing tail distributions. Thus, applications of the LSE-based regression models may be questioned for appropriateness and may have limited applicability. We have carried out the risk analysis of Iranian crude oil price data based on the Lp-norm regression models and have noted that the LSE-based models do not always perform the best. We discuss results from the L1, L2 and L∞-norm based linear regression models. ACM Computing Classification System (1998): B.1.2, F.1.3, F.2.3, G.3, J.2.

Regression games

The solution of a TU cooperative game can be a distribution of the value of the grand coalition, i.e. it can be a distribution of the payo (utility) all the players together achieve. In a regression model, the evaluation of the explanatory variables can be a distribution of the overall t, i.e. the t of the model every regressor variable is involved. Furthermore, we can take regression models as TU cooperative games where the explanatory (regressor) variables are the players. In this paper we introduce the class of regression games, characterize it and apply the Shapley value to evaluating the explanatory variables in regression models. In order to support our approach we consider Young (1985)'s axiomatization of the Shapley value, and conclude that the Shapley value is a reasonable tool to evaluate the explanatory variables of regression models.

Effectiveness of the Teaching Enrichment Activities to Minorities (TEAM) program at increasing underrepresented students in gifted programs

This study examined the effectiveness of the TEAM (Teaching Enrichment Activities to Minorities) program in preparing and identifying underrepresented students for entrance into the gifted program. Miami-Dade County Public Schools (M-DCPS) developed the TEAM program as an intervention program aimed at developing student's thinking skills and critical thinking skills in all subject areas and prepare students for possible placement into the gifted program. ^ A systematic sampling strategy was utilized to select three TEAM schools from each of the six regions in M-DCPS for the sample, for a total of 18 schools. A pool of the students that participated in the TEAM program in 2003-2004 in the 18 schools selected were identified as the TEAM Sample students. A matching sample was created from 18 public schools in Miami-Dade County that did not implement the TEAM program in 2003-2004. The Matching Sample created a match for 806 students in the TEAM sample, for a total of 1612 subjects for the study. ^ This study used a logistical regression design to analyze the relationships of multiple independent variables, including: ethnicity, limited English proficiency, gender, free/reduced lunch status, grade level, reading achievement, mathematics achievement, and participation TEAM on the dependent variables of referral for the gifted program and eligibility into the gifted program. The first analysis found the variables of grade level, participation in TEAM, reading achievement, and mathematics achievement were all significant variables in determining if a student was referred for the gifted program. The second analysis found the variables of grade level, gender, free/reduced lunch status, reading achievement, and mathematics achievement were all significant variables in determining if a student was eligible for the gifted program. ^ Recommendations based on the results of this study include the expansion of the TEAM program in M-DCPS to include additional grade levels and schools. Additionally, adopting a broadened definition of giftedness and reviewing the screening and placement policies for potentially gifted students is recommended. Adopting multicultural and broader definitions of giftedness and constructing better tools and programs, such as TEAM, for assessing and identifying potential gifted students, represent small steps towards creating equitable education for all students. ^

Quantifying the effects of temperature and concentration on variable-density flow in numerical modeling of groundwater systems: Implications for predictive uncertainty and data collection

Groundwater systems of different densities are often mathematically modeled to understand and predict environmental behavior such as seawater intrusion or submarine groundwater discharge. Additional data collection may be justified if it will cost-effectively aid in reducing the uncertainty of a model's prediction. The collection of salinity, as well as, temperature data could aid in reducing predictive uncertainty in a variable-density model. However, before numerical models can be created, rigorous testing of the modeling code needs to be completed. This research documents the benchmark testing of a new modeling code, SEAWAT Version 4. The benchmark problems include various combinations of density-dependent flow resulting from variations in concentration and temperature. The verified code, SEAWAT, was then applied to two different hydrological analyses to explore the capacity of a variable-density model to guide data collection. ^ The first analysis tested a linear method to guide data collection by quantifying the contribution of different data types and locations toward reducing predictive uncertainty in a nonlinear variable-density flow and transport model. The relative contributions of temperature and concentration measurements, at different locations within a simulated carbonate platform, for predicting movement of the saltwater interface were assessed. Results from the method showed that concentration data had greater worth than temperature data in reducing predictive uncertainty in this case. Results also indicated that a linear method could be used to quantify data worth in a nonlinear model. ^ The second hydrological analysis utilized a model to identify the transient response of the salinity, temperature, age, and amount of submarine groundwater discharge to changes in tidal ocean stage, seasonal temperature variations, and different types of geology. The model was compared to multiple kinds of data to (1) calibrate and verify the model, and (2) explore the potential for the model to be used to guide the collection of data using techniques such as electromagnetic resistivity, thermal imagery, and seepage meters. Results indicated that the model can be used to give insight to submarine groundwater discharge and be used to guide data collection. ^

Effect of performance feedback on perceived knowledge and likelihood to pursue continuing education

The purpose of this study was to assess the effect of performance feedback on Athletic Trainers’ (ATs) perceived knowledge (PK) and likelihood to pursue continuing education (CE). The investigation was grounded in the theories of “the definition of the situation” (Thomas & Thomas, 1928) and the “illusion of knowing,” (Glenberg, Wilkinson, & Epstein, 1982) suggesting that PK drives behavior. This investigation measured the degree to which knowledge gap predicted CE seeking behavior by providing performance feedback designed to change PK. A pre-test post-test control-group design was used to measure PK and likelihood to pursue CE before and after assessing actual knowledge. ATs (n=103) were randomly sampled and assigned to two groups, with and without performance feedback. Two independent samples t-tests were used to compare groups on the difference scores of the dependent variables. Likelihood to pursue CE was predicted by three variables using multiple linear regression: perceived knowledge, pre-test likelihood to pursue CE, and knowledge gap. There was a 68.4% significant difference (t101=2.72, p=0.01, ES=0.45) between groups in the change scores for likelihood to pursue CE because of the performance feedback (Experimental group=13.7% increase; Control group=4.3% increase). The strongest relationship among the dependent variables was between pre-test and post-test measures of likelihood to pursue CE (F2,102=56.80, p<0.01, r=0.73, R2=0.53). The pre- and post-test predictive relationship was enhanced when group was included in the model. In this model [YCEpost=0.76XCEpre-0.34 Xgroup+2.24+E], group accounted for a significant amount of unique variance in predicting CE while the pre-test likelihood to pursue CE variable was held constant (F3,102=40.28, p<0.01, r=0.74, R2=0.55). Pre-test knowledge gap, regardless of group allocation, was a linear predictor of the likelihood to pursue CE (F1,102=10.90, p=.01, r=.31, R2=.10). In this investigation, performance feedback significantly increased participants’ likelihood to pursue CE. Pre-test knowledge gap was a significant predictor of likelihood to pursue CE, regardless if performance feedback was provided. ATs may have self-assessed and engaged in internal feedback as a result of their test-taking experience. These findings indicate that feedback, both internal and external, may be necessary to trigger CE seeking behavior.

Variable responses within epiphytic and benthic microalgal communities to nutrient enrichment

We examined the spatial extent of nitrogen (N) and phosphorus (P) limitation of each of the major benthic primary producer groups in Florida Bay (seagrass, epiphytes, macroalgae, and benthic microalgae) and characterized the shifts in primary producer community composition following nutrient enrichment. We established 24 permanent 0.25-m2 study plots at each of six sites across Florida Bay and added N and P to the sediments in a factorial design for 18 mo. Tissue nutrient content of the turtlegrass Thalassia testudinum revealed a spatial pattern in P limitation, from severe limitation in the eastern bay (N:P > 96:1), moderate limitation in two intermediate sites (approximately 63:1), and balanced with N availability in the western bay (approximately 31:1). P addition increased T. testudinum cover by 50-75% and short-shoot productivity by up to 100%, but only at the severely P-limited sites. At sites with an ambient N:P ratio suggesting moderate P limitation, few seagrass responses to nutrients occurred. Where ambient T. testudinum tissue N:P ratios indicated N and P availability was balanced, seagrass was not affected by nutrient addition but was strongly influenced by disturbance (currents, erosion). Macroalgal and epiphytic and benthic microalgal biomass were variable between sites and treatments. In general, there was no algal overgrowth of the seagrass in enriched conditions, possibly due to the strength of seasonal influences on algal biomass or regulation by grazers. N addition had little effect on any benthic primary producers throughout the bay. The Florida Bay benthic primary producer community was P limited, but P-induced alterations of community structure were not uniform among primary producers or across Florida Bay and did not always agree with expected patterns of nutrient limitation based on stoichiometric predictions from field assays of T. testudinum tissue N:P ratios.

Temporally dependent C, N, and P dynamics associated with the decay of Rhizophora mangle L. leaf litter in oligotrophic mangrove wetlands of the Southern Everglades

We performed two litter decomposition experiments using nearly-senesced red mangrove (Rhizophora mangle L.) leaves collected from an Everglades dwarf mangrove wetland to understand the short-term (3 weeks) and long-term (1 year) changes in mass, as well as C-, N-, and P-content of decomposing leaf litter. We expected that leaves decomposing in this oligotrophic environment would be short-term sources of C, N, and P, but potential long-term sinks for N and P. In May 1998, we conducted a 3-week leaching experiment, incubating fresh, individual leaves in seawater for up to 21 days. From May 1997 to May 1998, leaf litter in mesh bags decomposed on the forest floor at two dwarf mangrove sites. Leaching accounted for about 33% loss of dry mass from R. mangle leaves after 3 weeks. Leaching losses were rapid, peaking by day 2, and large, with leachate concentrations of total organic carbon (TOC) and total phosphorus (TP) increasing by more than an order of magnitude after 3 weeks. Mean leaf C:N increased from 105 to 115 and N:P increased from a mean of 74 to 95 after 21 days, reflecting the relatively large leaching losses of N and P. Loss of mass in the litterbags leveled off after 4 months, with roughly 60%dry mass remaining (DMR) after nearly 1 year of decomposition. The mass of carbon in each litterbag declined significantly after 361 days, but the mass of nitrogen and phosphorus doubled, indicating long-term accumulation of these constituents into the detritus. Subsequently, the leaf C:N ratio dropped significantly from 90 to 34 after 361 days. Following an initial 44-day increase, leaf N:P decreased from 222 to 144, reflecting high accumulation of P relative to N. A review of several estuarine macrophyte decomposition studies reveals a trend in nitrogen accumulation through time regardless of site, but suggests no clear pattern for C and P. We believe that the increase in litter P observed in this study was indicative of the P-limited status of the greater Everglades ecosystem and that decomposing mangrove litter may represent a substantial phosphorus pool in the system.

The epidemiology of prostate cancer among multiethnic men

The research goal was to document differences in the epidemiology of prostate cancer among multicultural men [non-Hispanic White (NHW), Hispanic (H), non-Hispanic Black (NHB)], and Black subgroups, particularly among NHB subgroups [US-born (USB) and Caribbean-born (CBB)]. Study findings will be useful in supporting further research into Black subgroups. Aim 1 explored changes over time in reported prostate cancer prevalence, by race/ethnicity and by birthplace (within the Black subgroups). Aim 2 investigated relationships between observed and latent variables. The analytical approaches included confirmatory factor analysis (CFA for measurement models) and structural equation modeling (SEM for regression models). National Center for Health Statistics, National Health Interview Survey (NHIS) data from 1999–2008 were used. The study sample included men aged 18 and older, grouped by race/ethnicity. Among the CBB group, survey respondents were limited to the English-speaking Caribbean. Prostate cancer prevalence, by race showed a higher trend among NHB men than NHW men overall, however differences over time were not significant. CBB men reported a higher proportion of prostate cancer among cancers diagnosed than USB men overall. Due to small sample sizes, stable prostate cancer prevalence trends could not be assessed over time nor could trends in the receipt of a PSA exam among NHB men when stratified by birthplace. USB and CBB men differ significantly in their screening behavior. The effect of SES on PSA screening adjusted for risk factors was statistically significant while latent variable lifestyle was not. Among risk factors, family history of cancer exhibited a consistent positive effect on PSA screening for both USB and CBB men. Among the CBB men, the number of years lived in the US did not significantly affect PSA screening behavior. When NHB men are stratified by birthplace, CBB men had a higher overall prevalence of prostate cancer diagnoses than USB men although not statistically significant. USB men were 2 to 3 times more likely to have had a PSA exam compared to CBB men, but among CBB men birthplace did not make a significant difference in screening behavior. Latent variable SES, but not lifestyle, significantly affected the likelihood of a PSA exam.

Tree Mortality following Prescribed Fire and a Storm Surge Event in Slash Pine (Pinus elliottii var. densa) Forests in the Florida Keys, USA

In fire-dependent forests, managers are interested in predicting the consequences of prescribed burning on postfire tree mortality. We examined the effects of prescribed fire on tree mortality in Florida Keys pine forests, using a factorial design with understory type, season, and year of burn as factors. We also used logistic regression to model the effects of burn season, fire severity, and tree dimensions on individual tree mortality. Despite limited statistical power due to problems in carrying out the full suite of planned experimental burns, associations with tree and fire variables were observed. Post-fire pine tree mortality was negatively correlated with tree size and positively correlated with char height and percent crown scorch. Unlike post-fire mortality, tree mortality associated with storm surge from Hurricane Wilma was greater in the large size classes. Due to their influence on population structure and fuel dynamics, the size-selective mortality patterns following fire and storm surge have practical importance for using fire as a management tool in Florida Keys pinelands in the future, particularly when the threats to their continued existence from tropical storms and sea level rise are expected to increase.

Relative roles of dispersal dynamics and competition in determining the isotopic niche breadth of a wetland fish

1. The niche variation hypothesis predicts that among-individual variation in niche use will increase in the presence of intraspecific competition and decrease in the presence of interspecific competition. We sought to determine whether the local isotopic niche breadth of fish inhabiting a wetland was best explained by competition for resources and the niche variation hypothesis, by dispersal of individuals from locations with different prey resources or by a combination of the two. We analysed stable isotopes of carbon and nitrogen as indices of feeding niche and compared metrics of within-site spread to characterise site-level isotopic niche breadth. We then evaluated the explanatory power of competing models of the direct and indirect effects of several environmental variables spanning gradients of disturbance, competition strength and food availability on among-individual variation of the eastern mosquitofish (Gambusia holbrooki). 2. The Dispersal model posits that only the direct effect of disturbance (i.e. changes in water level known to induce fish movement) influences among-individual variation in isotopic niche. The Partitioning model allows for only direct effects of local food availability on among-individual variation. The Combined model allows for both hypotheses by including the direct effects of disturbance and food availability. 3. A linear regression of the Combined model described more variance than models limited to the variables of either the Dispersal or Partitioning models. Of the independent variables considered, the food availability variable (per cent edible periphyton) explained the most variation in isotopic niche breadth, followed closely by the disturbance variable (days since last drying event). 4. Structural equation modelling provided further evidence that the Combined model was best supported by the data, with the Partitioning and the Dispersal models only modestly less informative. Again, the per cent edible periphyton was the variable with the largest direct effect on niche variability, with other food availability variables and the disturbance variable only slightly less important. Indirect effects of heterospecific and conspecific competitor densities were also important, through their effects on prey density. 5. Our results support the Combined hypotheses, although partitioning mechanisms appear to explain the most diet variation among individuals in the eastern mosquitofish. The results also support some predictions of the niche variation hypothesis, although both conspecific and interspecific competition appeared to increase isotopic niche breadth in contrast to predictions that interspecific competition would decrease it. We think this resulted from high diet overlap of co-occurring species, most of which consume similar macroinvertebrates.

Boundary Effects on Benthic Microbial Phosphorus Concentrations and Diatom Beta Diversity in a Hydrologically-modified, Nutrient-limited Wetland

Water flow and flooding duration in wetlands influence the structure and productivity of microbial communities partly through their influence on nutrient loading. The effect of flow-regulated nutrient loads is especially relevant for microbial communities in nutrient-poor settings, where delivery controls nutrient uptake rates and the intensity of microbial interactions. We examined the effect of hydrologic history and proximity to water sources on nutrient enrichment of benthic microbial assemblages (periphyton) and on their diatom species composition, along the artificial boundaries of Taylor Slough, a historically phosphorus-depleted drainage of the Florida Everglades. Concentrations of phosphorus in periphyton declined from the wetland boundary near inflow structures to 100-m interior, with spatial and temporal variability in rates dependent on proximity to and magnitude of water flow. Phosphorus availability influenced the beta diversity of diatom assemblages, with higher values near inflow structures where resources were greatest, while interior sites and reference transects contained assemblages with constant composition of taxa considered endemic to the Everglades. This research shows how hydrologic restoration may have unintended consequences when incoming water quality is not regulated, including a replacement of distinctive microbial assemblages by ubiquitous, cosmopolitan ones.

The mosses of Terra Nova National Park, Eastern Newfoundland, a bryofloristic analysis and interpretation

The known moss flora of Terra Nova National Park, eastern Newfoundland, comp~ises 210 species. Eighty-two percent of the moss species occurring in Terra Nova are widespread or widespread-sporadic in Newfoundland. Other Newfoundland distributional elements present in the Terra Nova moss flora are the northwestern, southern, southeastern, and disjunct elements, but four of the mosses occurring in Terra Nova appear to belong to a previously unrecognized northeastern element of the Newfoundland flora. The majority (70.9%) of Terra Nova's mosses are of boreal affinity and are widely distributed in the North American coniferous forest belt. An additional 10.5 percent of the Terra Nova mosses are cosmopolitan while 9.5 percent are temperate and 4.8 percent are arctic-montane species. The remaining 4.3 percent of the mosses are of montane affinity, and disjunct between eastern and western North America. In Terra Nova, temperate species at their northern limit are concentrated in balsam fir stands, while arctic-montane species are restricted to exposed cliffs, scree slopes, and coastal exposures. Montane species are largely confined to exposed or freshwater habitats. Inability to tolerate high summer temperatures limits the distributions of both arctic-montane and montane species. In Terra Nova, species of differing phytogeographic affinities co-occur on cliffs and scree slopes. The microhabitat relationships of five selected species from such habitats were evaluated by Discriminant Functions Analysis and Multiple Regression Analysis. The five mosses have distinct and different microhabitats on cliffs and scree slopes in Terra Nova, and abundance of all but one is associated with variation in at least one microhabitat variable. Micro-distribution of Grimmia torquata, an arctic-montane species at its southern limit, appears to be deterJ]lined by sensitivity to high summer temperatures. Both southern mosses at their northern limit (Aulacomnium androgynum, Isothecium myosuroides) appear to be limited by water availability and, possibly, by low winter temperatures. The two species whose distributions extend both north and south or the study area (Encalypta procera, Eurhynchium pulchellum) show no clear relationship with microclimate. Dispersal factors have played a significant role in the development of the Terra Nova moss flora. Compared to the most likely colonizing source (i .e. the rest of the island of Newfoundland), species with small diaspores have colonized the study area to a proportionately much greater extent than have species with large diaspores. Hierarchical log-linear analysis indicates that this is so for all affinity groups present in Terra Nova. The apparent dispersal effects emphasize the comparatively recent glaciation of the area, and may also have been enhanced by anthropogenic influences. The restriction of some species to specific habitats, or to narrowly defined microhabitats, appears to strengthen selection for easily dispersed taxa.

Fixed vs. variable noise in 2AFC contrast discrimination: lessons from psychometric functions.

Recent discussion regarding whether the noise that limits 2AFC discrimination performance is fixed or variable has focused either on describing experimental methods that presumably dissociate the effects of response mean and variance or on reanalyzing a published data set with the aim of determining how to solve the question through goodness-of-fit statistics. This paper illustrates that the question cannot be solved by fitting models to data and assessing goodness-of-fit because data on detection and discrimination performance can be indistinguishably fitted by models that assume either type of noise when each is coupled with a convenient form for the transducer function. Thus, success or failure at fitting a transducer model merely illustrates the capability (or lack thereof) of some particular combination of transducer function and variance function to account for the data, but it cannot disclose the nature of the noise. We also comment on some of the issues that have been raised in recent exchange on the topic, namely, the existence of additional constraints for the models, the presence of asymmetric asymptotes, the likelihood of history-dependent noise, and the potential of certain experimental methods to dissociate the effects of response mean and variance.

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.

UNLABELLED: Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response. IMPORTANCE: Infants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1-transmitting and -nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope proteins were associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding and the development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation.