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Observation datasets acquired by the Hyper Suprime-Cam (HSC) on the Subaru Telescope for NASA's New Horizons mission target search were analyzed through a method devised by JAXA. The method makes use of Field Programmable Gate arrays and was originally used to detect fast-moving objects such as space debris or near-Earth asteroids. Here we present an application of the method to detect slow-moving Kuiper Belt Objects (KBOs) in the New Horizons target search observations. A cadence that takes continuous images of one HSC field of view for half a night fits the method well. The observations for the New Horizons Kuiper Belt Extended Mission (NH/KEM) using HSC began in 2020 May, and are ongoing. Here we show our result of the analysis of the dataset acquired from 2020 May through 2021 June that have already passed the proprietary period and are open to the public. We detected 84 KBO candidates in the 2020 June and 2021 June datasets, when the observation field was close to opposition. [ABSTRACT FROM AUTHOR]

Understanding the dynamics of intracellular signaling pathways, such as ERK1/2 (ERK) and Akt1/2 (Akt), in the context of cell fate decisions is important for advancing our knowledge of cellular processes and diseases, particularly cancer. While previous studies have established associations between ERK and Akt activities and proliferative cell fate, the heterogeneity of single-cell responses adds complexity to this understanding. This study employed a data-driven approach to address this challenge, developing machine learning models trained on a dataset of growth factor-induced ERK and Akt activity time courses in single cells, to predict cell division events. The most predictive models were developed by applying discrete wavelet transforms (DWTs) to extract low-frequency features from the time courses, followed by using Ensemble Integration, a data integration and predictive modeling framework. The results demonstrated that these models effectively predicted cell division events in MCF10A cells (F-measure=0.524, AUC=0.726). ERK dynamics were found to be more predictive than Akt, but the combination of both measurements further enhanced predictive performance. The ERK model's performance also generalized to predicting division events in RPE cells, indicating the potential applicability of these models and our data-driven methodology for predicting cell division across different biological contexts. Interpretation of these models suggested that ERK dynamics throughout the cell cycle, rather than immediately after growth factor stimulation, were associated with the likelihood of cell division. Overall, this work contributes insights into the predictive power of intra-cellular signaling dynamics for cell fate decisions, and highlights the potential of machine learning approaches in unraveling complex cellular behaviors. [ABSTRACT FROM AUTHOR]

High‐quality, gridded maps of crop yield, which discern the spatial variability in productivity across individual farm fields, are extremely valuable in numerous agricultural and remote sensing applications. The availability of these data was greatly facilitated by the development and adoption of grain yield monitors starting in the early 1990s. However, the utility of raw yield monitor data is limited if additional processing has not been carried out to ensure data quality. In addition, a readily accessible data repository that allows for examining long‐term yield variability in response to climate and management is often not available. We present a protocol for producing a multi‐year (7 years currently processed), gridded yield data archive derived from yield monitor data acquired from over 40 production fields at the Beltsville Agricultural Research Center (BARC) in Beltsville, MD. Production of the archive involved the projection of the yield monitor data into a geographic coordinate system suitable for mapping, the identification and removal of data outliers, and the production of gridded, spatially interpolated yield maps using block Kriging. All map products were produced in common, nonproprietary file formats for easy access. Preliminary assessments of the processed yield monitor data have underscored the necessity of data filtering and have shown the influence of previous land use practices and biophysical properties, such as topography and soil moisture availability, on yield response. We discuss the use of spatially interpolated, archival yield maps in the implementation of precision farming techniques such as the development of site‐specific variable rate prescriptions as well as remote sensing applications, including the selection of field sites for long‐term agricultural experiments and the assessment of crop modeling approaches. The gridded yield data archive will be housed at the National Agricultural Library as a dynamic dataset that will continue to expand in breadth and depth. It will be a part of and provide support to internal USDA yield monitoring investigations as well as complementary external efforts. All geospatial data delivered to NAL will adhere to the ISO 19115 Geospatial Metadata Standards to provide the user with a full understanding of the yield monitor and associated datasets.Core Ideas: Yield monitor data often go unprocessed and unorganized.A protocol is presented for the creation of a spatially interpolated yield data archive.Use of yield data archive in precision farming and agricultural field experiments is explored. [ABSTRACT FROM AUTHOR]

The integrity of the barrier between blood and the selective filtrate of solutes is important for homeostasis and its disruption contributes to many diseases. Microphysiological systems that incorporate synthetic or natural membranes with human cells can mimic biological filtration barriers, such as the glomerular filtration barrier in the kidney, and they can readily be used to study cellular filtration processes as well as drug effects and interactions. We present an affordable, open-source platform for the real-time monitoring of functional filtration status in engineered microphysiological systems. Using readily available components, our assay can linearly detect real-time concentrations of two target molecules, FITC-labeled inulin and Texas Red-labeled human-serum albumin, within clinically relevant ranges, and it can be easily modified for different target molecules of varying sizes and tags. We demonstrate the platform's ability to determine the concentration of our target molecules automatically and consistently. We show through an acellular context that the platform enables real-time tracking of size-dependent diffusion with minimal fluid volume loss and without manual extraction of media, making it suitable for continuous operational monitoring of filtration status in microphysiological system applications. The platform's affordability and integrability with microphysiological systems make it ideal for many precision medicine applications, including evaluation of drug nephrotoxicity and other forms of drug discovery. [ABSTRACT FROM AUTHOR]

Determining residue cover on agricultural land is an important task. Residue cover helps reduce soil erosion and helps sequester carbon. Many studies have used either spectral indices or classification techniques to map residue cover using satellite imagery. Unfortunately, most of these studies use only a few spectral indices or classification techniques and generally only study an area for a single year with a certain level of success. This manuscript presents an investigation of five spectral indices and six classification techniques over four years to determine if a single spectral index or classification technique performs consistently better than the others. A second objective is to determine whether using the coefficient of determination (R2) from the relationship between residue cover and a spectral index is a reasonable substitute for calculating accuracy. Field visits were conducted for each of the years studied and used to create the correlations with the spectral indices and as ground truth for the classification techniques. It was found that no spectral index/classification technique is consistently better than all the others. Classification techniques tended to be more accurate in 2011 and 2013, while spectral indices tended to be more accurate in 2015 and 2018. The combination of spectral indices/classification techniques outperformed the individual approach. For the second objective, it was found that R2 is not a great indicator of accuracy. Root mean square error (RMSE) is a better indicator of accuracy than R2. However, simply calculating the accuracy would be the best of all. [ABSTRACT FROM AUTHOR]

Networks underlie much of biology from subcellular to ecological scales. Yet, understanding what experimental data are needed and how to use them for unambiguously identifying the structure of even small networks remains a broad challenge. Here, we integrate a dynamic least squares framework into established modular response analysis (DL-MRA), that specifies sufficient experimental perturbation time course data to robustly infer arbitrary two and three node networks. DL-MRA considers important network properties that current methods often struggle to capture: (i) edge sign and directionality; (ii) cycles with feedback or feedforward loops including self-regulation; (iii) dynamic network behavior; (iv) edges external to the network; and (v) robust performance with experimental noise. We evaluate the performance of and the extent to which the approach applies to cell state transition networks, intracellular signaling networks, and gene regulatory networks. Although signaling networks are often an application of network reconstruction methods, the results suggest that only under quite restricted conditions can they be robustly inferred. For gene regulatory networks, the results suggest that incomplete knockdown is often more informative than full knockout perturbation, which may change experimental strategies for gene regulatory network reconstruction. Overall, the results give a rational basis to experimental data requirements for network reconstruction and can be applied to any such problem where perturbation time course experiments are possible. [ABSTRACT FROM AUTHOR]

Biochemical correlates of stochastic single-cell fates have been elusive, even for the well-studied mammalian cell cycle. We monitored single-cell dynamics of the ERK and Akt pathways, critical cell cycle progression hubs and anti-cancer drug targets, and paired them to division events in the same single cells using the non-transformed MCF10A epithelial line. Following growth factor treatment, in cells that divide both ERK and Akt activities are significantly higher within the S-G2 time window (~ 8.5–40 h). Such differences were much smaller in the pre-S-phase, restriction point window which is traditionally associated with ERK and Akt activity dependence, suggesting unappreciated roles for ERK and Akt in S through G2. Simple metrics of central tendency in this time window are associated with subsequent cell division fates. ERK activity was more strongly associated with division fates than Akt activity, suggesting Akt activity dynamics may contribute less to the decision driving cell division in this context. We also find that ERK and Akt activities are less correlated with each other in cells that divide. Network reconstruction experiments demonstrated that this correlation behavior was likely not due to crosstalk, as ERK and Akt do not interact in this context, in contrast to other transformed cell types. Overall, our findings support roles for ERK and Akt activity throughout the cell cycle as opposed to just before the restriction point, and suggest ERK activity dynamics may be more important than Akt activity dynamics for driving cell division in this non-transformed context. [ABSTRACT FROM AUTHOR]

Most cancer cells harbor multiple drivers whose epistasis and interactions with expression context clouds drug and drug combination sensitivity prediction. We constructed a mechanistic computational model that is context-tailored by omics data to capture regulation of stochastic proliferation and death by pan-cancer driver pathways. Simulations and experiments explore how the coordinated dynamics of RAF/MEK/ERK and PI-3K/AKT kinase activities in response to synergistic mitogen or drug combinations control cell fate in a specific cellular context. In this MCF10A cell context, simulations suggest that synergistic ERK and AKT inhibitor-induced death is likely mediated by BIM rather than BAD, which is supported by prior experimental studies. AKT dynamics explain S-phase entry synergy between EGF and insulin, but simulations suggest that stochastic ERK, and not AKT, dynamics seem to drive cell-to-cell proliferation variability, which in simulations is predictable from pre-stimulus fluctuations in C-Raf/B-Raf levels. Simulations suggest MEK alteration negligibly influences transformation, consistent with clinical data. Tailoring the model to an alternate cell expression and mutation context, a glioma cell line, allows prediction of increased sensitivity of cell death to AKT inhibition. Our model mechanistically interprets context-specific landscapes between driver pathways and cell fates, providing a framework for designing more rational cancer combination therapy. [ABSTRACT FROM AUTHOR]

Mass cytometry offers the advantage of allowing the simultaneous measurement of a greater number parameters than conventional flow cytometry. However, to date, mass cytometry has lacked a reliable alternative to the light scatter properties that are commonly used as a cell size metric in flow cytometry (forward scatter intensity-FSC). Here, we report the development of two plasma membrane staining assays to evaluate mammalian cell size in mass cytometry experiments. One is based on wheat germ agglutinin (WGA) staining and the other on Osmium tetroxide (OsO4) staining, both of which have preferential affinity for cell membranes. We first perform imaging and flow cytometry experiments to establish a relationship between WGA staining intensity and traditional measures of cell size. We then incorporate WGA staining in mass cytometry analysis of human whole blood and show that WGA staining intensity has reproducible patterns within and across immune cell subsets that have distinct cell sizes. Lastly, we stain PBMCs or dissociated lung tissue with both WGA and OsO4 ; mass cytometry analysis demonstrates that the two staining intensities correlate well with one another. We conclude that both WGA and OsO4 may be used to acquire cell size-related parameters in mass cytometry experiments, and expect these stains to be broadly useful in expanding the range of parameters that can be measured in mass cytometry experiments. © 2016 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Although all chromite ore processing residue (COPR) sites near residential neighborhoods in Jersey City, New Jersey have undergone remediation, recent studies found widespread, but low levels of hexavalent chromium (Cr+6) in house dust both in Jersey City and in communities with no known sources of Cr+6. This study was designed as a follow-up to determine whether there is an association between current Cr+6 levels in house dust and urinary chromium concentrations in young children. Dust samples (N=369) were collected from 123 homes. The median Cr+6 concentration was 3.3 μg/g (mean±SD 5.2±7.5) and the median Cr+6 loading was 1.1 μg/m2 (1.9±3.1). These levels were not elevated compared with previously reported levels in background communities (median concentration=3.5 μg/g; median loading=2.8 μg/m2). Urinary chromium concentrations were measured in spot urine samples collected from 150 children, ages 3 months to 6 years. The median uncorrected urinary chromium concentration was 0.19 μg/l (0.22±0.16). Current urinary chromium concentrations were significantly lower than those previously reported before and during remediation (t-test; P<0.001). Urinary chromium concentrations were not significantly higher in homes with high (75th or 90th percentile) Cr+6 dust levels (concentration or loading) compared with other homes. Multiple linear regression was used to examine the relationship between Cr+6 levels (concentration and loading) in house dust and urinary chromium concentrations (uncorrected and specific gravity corrected). Contrary to pre-remediation studies, we did not find a positive association between Cr+6 levels in house dust and urinary chromium concentrations. The findings indicate that current Cr+6 levels in house dust are not positively associated with children's chromium exposure as measured by urinary chromium, and the children's exposure to Cr+6 in house dust is below the level that could be identified by urine sampling. [ABSTRACT FROM AUTHOR]

Compressed sensing (CS) has attracted a great deal of recent interest as an approach for spectrum analysis of nonuniformly sampled NMR data. Although theoretical justification for the method is abundant, it suffers from several weaknesses, among them poor convergence of some algorithms, and it remains an open question whether NMR spectra satisfy the sparsity requirements of CS theorems. The versions of CS used in NMR involve minimizing the l1 norm of the spectrum. They bear similarity to maximum entropy (MaxEnt) reconstruction, but critical comparison of the methods can be difficult. Here we describe a formalism that places CS and MaxEnt reconstruction on equal footing, enabling critical comparison of the two methods. We also describe a new algorithm for CS that restricts the computation of the l1 norm to the real channel for complex spectra and ensures causality. Preliminary 1D results demonstrate that this approach ameliorates some artifacts that can occur when using the l1 norm of the complex spectrum. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Standard data products from NASA’s moderate resolution imaging spectroradiometer (MODIS) were available at launch (collection 3) and have undergone two revisions (collections 4 and 5) during the continuing Terra and Aqua missions. In 2000, a research project was conducted in large fields of corn and soybean to evaluate MODIS leaf area index (LAI) and land cover type (MOD15 and MOD12 data products, respectively) as input to crop yield models. Our objective was to compare collections 3, 4 and 5 with the ground data to determine data product improvement. Classification of land cover type for collections 3, 4 and 5 were similar to the USDA-NASS Cropland Data Layer. The collection 5 MOD15 LAI was considerably improved over earlier collections when the quality assurance flags indicated good LAI retrievals. Land surface reflectances (MOD09) of MODIS band 2 (near-infrared, 250-m) were used as inputs to an inversion of the scattering by arbitrarily inclined leaves (SAIL) model. Compared to the collection 5 MOD15 product, SAIL-derived LAI had approximately equal agreement with the field data and had less systematic bias in root mean square error (RMSE). MODIS data products were designed to address global scientific questions without reliance on ground data, whereas the SAIL model inversions required ground data for model inputs. The accuracy of MODIS observations was not limiting LAI accuracy for broadleaf crops; additional information from non-MODIS sources may be required for improved MOD15 LAI. [ABSTRACT FROM AUTHOR]

During much of the twentieth century, Jersey City, New Jersey was the leading center of chromate production in the United States. Chromate production produced huge volumes of chromium ore-processing residue containing many parts per million of hexavalent chromium. Starting in the 1990s, we undertook a series of studies to identify exposed populations, sources and pathways of exposure and the effectiveness of remediation activities in Jersey City. These studies revealed the effectiveness and success of the remediation activities. The sequence of studies presented here, builds on the lessons learned from each preceding study and illustrates how these studies advanced the field of exposure science in important ways, including the use of household dust as a measure of exposure to contaminants originating in the outdoor environment; development of effective and reproducible dust sampling; use of household dust to track temporal changes in exposure; understanding of the spatial relationship between sources of passive outdoor particulate emissions and residential exposure; use of focused biomonitoring to assess exposure under conditions of large inter-individual variability; and utility of linking environmental monitoring and biomonitoring. For chromium, the studies have demonstrated the use of Cr+6-specific analytical methods for measuring low concentrations of Cr+6 in household dust and understanding of the occurrence of Cr+6 in the background residential environment. We strongly recommend that environmental and public health agencies evaluate sites for their potential for off-site exposure and apply these tools in cases with significant potential as appropriate. This approach is especially important when contamination is widespread and/or a large population is potentially exposed. In such cases, these tools should be used to identify, characterize and then reduce the exposure to the off-site as well as on-site population. Importantly, these tools can be used in a demonstrable and quantifiable manner to provide both clarity and closure to concerned stakeholders. [ABSTRACT FROM AUTHOR]

Background: Toenail-Hg levels are being used as a marker of methylmercury (MeHg) exposure in efforts to associate exposure with effects such as cardiovascular disease. There is a need to correlate this marker with more established biomarkers that presently underlie existing dose-response relationships in order to compare these relationships across studies. Methods: As part of the Arsenic Mercury Intake Biometric Study, toenail clippings were collected at three time points over a period of one year amongst females from within the population of Japanese living near Puget Sound in Washington State (US). Variability in temporal intra-individual toenail-Hg levels was examined and chronologically matched hair and toenail samples were compared to more accurately define the toxicokinetic variability of Hg levels observed between the two compartments. Results: Mean toenail-Hg values (n=43) for the 1st, 2nd and 3rd visits were 0.60, 0.60 and 0.56 ng/mg. Correlations were as follows: r=0.92 between 1st and 2nd clinic visits, r=0.75 between 1st and 3rd visits and r=0.87 between 2nd and 3rd visits. With few exceptions, toenail-Hg values from any visit were within 50-150% of the individual's mean toenail-Hg level. Nearly all participants had less than a two-fold change in toenail-Hg levels across the study period. A regression model of the relationship between toenail-Hg and hair-Hg (n = 41) levels representing the same time period of exposure, gave a slope (Hg ng/mg) of 2.79 for hair relative to toenail (r=0.954). Conclusions: A chronologically matched hair-Hg to toenail-Hg ratio has been identified within a population that consumes fish regularly and in quantity. Intra-individual variation in toenail-Hg levels was less than two-fold and may represent dietary-based fluctuations in body burden for individuals consuming various fish species with different contaminant levels. The chronologically matched ratio will be useful for relating MeHg exposure and dose-response derived from toenail-Hg measurements to those derived from hair-Hg measurements in other studies, and may be useful in future investigations as an indicator of stable MeHg body burden within a population. [ABSTRACT FROM AUTHOR]

Background: The most prominent non-occupational source of exposure to methylmercury is the consumption of fish. In this study we examine a fish consuming population to determine the extent of temporal exposure and investigate the extent to which single time estimates of methylmercury exposure based on blood-Hg concentration can provide reliable estimates of longer-term average exposure. Methods: Blood-mercury levels were obtained from a portion of the Arsenic Mercury Intake Biometric Study (AMIBS) cohort. Specifically, 56 Japanese women residing in the Puget Sound area of Washington State, US were sampled on three occasions across a one-year period. Results: An average of 135 days separated samples, with mean blood-mercury levels for the visits being 5.1, 6.6 and 5.0 μg/l and geometric means being 2.7, 4.5 and 3.1 μg/l. The blood-mercury levels in this group exceed national averages with geometric means for two of the visits being between the 90th and 95th percentiles of nationally observed levels and the lowest geometric mean being between the 75th and 90th percentile. Group means were not significantly different across sampling periods suggesting that exposure of combined subjects remained relatively constant. Comparing intra-individual results over time did not reveal a strong correlation among visits (r = 0.19, 0.50, 0.63 between 1st and 2nd, 2nd and 3rd, and 1st and 3rd sample results, respectively). In comparing blood-mercury levels across two sampling interval combinations (1st and 2nd, 2nd and 3rd, and 1st and 3rd visits, respectively), 58% (n = 34), 53% (n = 31) and 29% (n = 17) of the individuals had at least a 100% difference in blood-Hg levels. Conclusions: Point estimates of blood-mercury, when compared with three sample averages, may not reflect temporal variability and individual exposures estimated on the basis of single blood samples should be treated with caution as indicators of long-term exposure. Reliance on single blood samples can make predicting ongoing methylmercury exposure highly speculative due to the large intra-individual variability. [ABSTRACT FROM AUTHOR]

Despite advances in resolution accompanying the development of high-field superconducting magnets, biomolecular applications of NMR require multiple dimensions in order to resolve individual resonances, and the achievable resolution is typically limited by practical constraints on measuring time. In addition to the need for measuring long evolution times to obtain high resolution, the need to distinguish the sign of the frequency constrains the ability to shorten measuring times. Sign discrimination is typically accomplished by sampling the signal with two different receiver phases or by selecting a reference frequency outside the range of frequencies spanned by the signal and then sampling at a higher rate. In the parametrically sampled (indirect) time dimensions of multidimensional NMR experiments, either method imposes an additional factor of 2 sampling burden for each dimension. We demonstrate that by using a single detector phase at each time sample point, but randomly altering the phase for different points, the sign ambiguity that attends fixed single-phase detection is resolved. Random phase detection enables a reduction in experiment time by a factor of 2 for each indirect dimension, amounting to a factor of 8 for a four-dimensional experiment, albeit at the cost of introducing sampling artifacts. Alternatively, for fixed measuring time, random phase detection can be used to double resolution in each indirect dimension. Random phase detection is complementary to nonuniform sampling methods, and their combination offers the potential for additional benefits. In addition to applications in biomolecular NMR, random phase detection could be useful in magnetic resonance imaging and other signal processing contexts. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nearly all fish consumption advisories for methylmercury (MeHg) are based only on risk. There is a need to also address benefits, especially those from polyunsaturated fatty acids (PUFAs), in neurodevelopmental function and cardiovascular health. However, because MeHg and PUFA generally act on these same end points, disentangling risk and benefit is challenging. OBJECTIVES: We propose an approach for balancing risk and benefit that is based on the use of statistically dissociated measures of risk and benefit. DISCUSSION: Because of mutual coexposure of MeHg and PUFAs in population-based studies and their opposite effect on many of the same end points, MeHg risk and PUFA benefit are tightly linked statistically, which results in mutual (negative) confounding. Thus, neither MeHg risk nor PUFA benefit can be accurately quantified without taking the other into account. A statistical approach that generates unconfounded risk and benefit coefficients for each end point can permit their subsequent recombination to describe the overall risk-benefit profile of each species of fish or fish diet. However, it appears that some end points may be adversely affected by MeHg without experiencing counterbalancing benefit from PUFAs. Such end points may drive consumption advisories and may preclude balancing of risk and benefit on the basis of other end points. CONCLUSIONS: Our thinking about fish consumption advisories now recognizes the need to balance risk and benefit. However, although statistical analysis of the appropriate data can eliminate mutual confounding, care is required to address the most sensitive end points that may be sensitive to risk and not benefit. [ABSTRACT FROM AUTHOR]

Background: The U.S. Environmental Protection Agency (U.S. EPA) has estimated the neurological benefits of reductions in prenatal methylmercury (MeHg) exposure in past assessments of rules controlling mercury (Hg) emissions. A growing body of evidence suggests that MeHg exposure can also lead to increased risks of adverse cardiovascular impacts in exposed populations. Data extraction: The U.S. EPA assembled the authors of this article to participate in a workshop, where we reviewed the current science concerning cardiovascular health effects of MeHg exposure via fish and seafood consumption and provided recommendations concerning whether cardiovascular health effects should be included in future Hg regulatory impact analyses. Data synthesis: We found the body of evidence exploring the link between MeHg and acute myocardial infarction (MI) to be sufficiently strong to support its inclusion in future benefits analyses, based both on direct epidemiological evidence of an MeHg-MI link and on MeHg's association with intermediary impacts that contribute to MI risk. Although additional research in this area would be beneficial to further clarify key characteristics of this relationship and the biological mechanisms that underlie it, we consider the current epidemiological literature sufficiently robust to support the development of a dose-response function. Conclusions: We recommend the development of a dose-function relating MeHg exposures with MIs for use in regulatory benefits analyses of future rules targeting Hg air emissions. [ABSTRACT FROM AUTHOR]

The paper builds on existing literature, highlighting current understanding and identifying unresolved issues about MeHg exposure, health effects, and risk assessment, and concludes with a consensus statement. Methylmercury is a potent toxin, bioaccumulated and concentrated through the aquatic food chain, placing at risk people, throughout the globe and across the socioeconomic spectrum, who consume predatory fish or for whom fish is a dietary mainstay. Methylmercury developmental neurotoxicity has constituted the basis for risk assessments and public health policies. Despite gaps in our knowledge on new bioindicators of exposure, factors that influence MeHg uptake and toxicity, toxicokinetics, neurologic and cardiovascular effects in adult populations, and the nutritional benefits and risks from the large number of marine and freshwater fish and fish-eating species, the panel concluded that to preserve human health, all efforts need to be made to reduce and eliminate sources of exposure. [ABSTRACT FROM AUTHOR]

Historically, concerns with fish consumption have addressed risks from contaminants (e.g., methylmercury (MeHg), and PCBs). More recently public health concerns have widened in appreciation of the specific benefits of fish consumption such as those arising from polyunsaturated fatty acids (PUFAs) in fish oil. Fish contains varying levels of PUFAs and MeHg. Since both address the same health outcomes (in opposite directions) and occur together in fish, great care must be exercised in providing public health guidance. Mozaffarian and Rimm in a recent article (JAMA. 2006, 296:1885-99) have made a strong case for the beneficial effects of PUFAs in reducing the risk of coronary heart disease, but at the same time, have also broadly discounted the increased risks of coronary heart disease posed by MeHg in fish, stating that "... among adults... the benefits of fish intake exceed the potential risks." This conclusion appears to be based on an inaccurate and insufficiently critical analysis of the literature. This literature is re-examined in light of their conclusions, and the available and appropriate public health options are considered. [ABSTRACT FROM AUTHOR]

Elemental mercury has been imbued with magical properties for millennia, and various cultures use elemental mercury in a variety of superstitious and cultural practices, raising health concerns for users and residents in buildings where it is used. As a first step in assessing this phenomenon, we compared mercury vapor concentration in common areas of residential buildings versus outdoor air, in two New Jersey cities where mercury is available and is used in cultural practices. We measured mercury using a portable atomic absorption spectrometer capable of quantitative measurement from 2 ng/m3 mercury vapor. We evaluated the interior hallways in 34 multifamily buildings and the vestibule in an additional 33 buildings. Outdoor mercury vapor averaged 5 ng/m3; indoor mercury was significantly higher (mean 25 ng/m3; p < 0.001); 21% of buildings had mean mercury vapor concentration in hallways that exceeded the 95th percentile of outdoor mercury vapor concentration (17 ng/m3), whereas 35% of buildings had a maximum mercury vapor concentration that exceeded the 95th percentile of outdoor mercury concentration. The highest indoor average mercury vapor concentration was 299 ng/m3, and the maximum point concentration was 2,022 ng/m3. In some instances, we were able to locate the source, but we could not specifically attribute the elevated levels of mercury vapor to cultural use or other specific mercury releases. However, these findings provide sufficient evidence of indoor mercury source(s) to warrant further investigation. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor commenting on benefits of fish consumption.

We describe an efficient NMR triple resonance approach that correlates, at high resolution, protein side-chain and backbone resonances. It relies on the combination of two strategies: joint evolution of aliphatic side-chain proton/carbon coherences using a backbone N–H based HCcoNH reduced dimensionality (RD) experiment and non-uniform sampling (NUS) in two indirect dimensions. A typical data set containing such correlation information can be acquired in 2 days, at very high resolution unfeasible for conventional 4D HCcoNH-TOCSY experiments. The resonances of the aliphatic side-chain protons are unambiguously assigned to their attached carbons through the analysis of the ‘sum’ and ‘difference’ spectra. This approach circumvents the tedious process of manual resonance assignments using HCcH-TOCSY data, while providing additional resolving power of backbone N–H signals. A simple peak-list based algorithm has been implemented in the IBIS software for rapid automated backbone and side-chain assignments. [ABSTRACT FROM AUTHOR]

Most attention to the risks from fish consumption has focused on recreational anglers and on fish caught by individuals, but the majority of fish that people eat are purchased from commercial sources. We examined mercury levels in three types of fish (tuna, flounder, bluefish) commonly available in New Jersey stores, sampling different regions of the state, in communities with high and low per capita incomes, and in both supermarkets and specialty fish markets. We were interested in species-specific levels of mercury in New Jersey fish and whether these levels were similar to data generated nationally by the Food and Drug Administration (FDA; mainly from 1990 to 1992) on the same types of fish. Such information is critical for providing public health advice. We were also interested in whether mercury levels in three common species of fish differed by region of the state, economic neighborhood, or type of store. We found significant species differences, with tuna having the highest levels and flounder the lowest levels. There were no significant differences in mercury levels as a function of type of store or economic neighborhood. There was only one regional difference: flounder from fish markets along the Jersey shore had higher mercury levels than flounder bought in other markets. We also examined mercury levels in six other commonly available fish and two shellfish from central New Jersey markets. There were significant differences in availability and in mercury levels among fish and shellfish. Both shrimp and scallops had total mercury levels < 0.02 ppm (wet weight). Large shrimp had significantly lower levels of mercury than small shrimp. For tuna, sea bass, croaker, whiting, scallops, and shrimp, the levels of mercury were higher in New Jersey samples than those reported by the FDA. Consumers selecting fish for ease of availability (present in > 50% of markets) would select flounder, snapper, bluefish, and tuna (tuna had the highest mercury value), and those selecting only for price would select whiting, porgy, croaker, and bluefish (all with average mercury levels < 0.3 ppm wet weight). Flounder was the fish with the best relationship among availability, cost, and low mercury levels. We suggest that state agencies responsible for protecting the health of their citizens should obtain information on fish availability in markets and fish preferences of diverse groups of citizens and use this information to select fish for analysis of contaminant levels, providing data on the most commonly eaten fish that will help people make informed decisions about risks from fish consumption. [ABSTRACT FROM AUTHOR]

In 2001, the U.S. Environmental Protection Agency (EPA) adopted a revised reference dose (RfD) for methyl mercury (MeHg) of 0.1 μg/kg/day. The RfD is based on neurologic developmental effects measured in children associated with exposure in uztero to MeHg from the maternal diet. The RfD derivation proceeded from a point of departure based on measured concentration of mercury in fetal cord blood (micrograms per liter). The RID, however, is a maternal dose (micro- grams per kilogram per day). Reconstruction of the maternal dose corresponding to this cord blood concentration, including the variability around this estimate, is a critical step in the RID derivation. The dose reconstruction employed by the U.S. EPA using the one-compartment phar-macokinetic model contains two areas of significant uncertainty: It does not directly account for the influence of the ratio of cord blood:maternal blood Hg concentration, and it does not resolve uncertainty regarding the most appropriate central tendency estimates for pregnancy and third- trimester-specific model parameters. A probabilistic reassessment of this dose reconstruction was undertaken to address these areas of uncertainty and generally to reconsider the specification of model input parameters. On the basis of a thorough review of the literature and recalculation of the one-compartment model including sensitivity analyses, I estimated that the 95th and 99th percentiles (i.e., the lower 5th and 1st percentiles) of the maternal intake dose corresponding to a fetal cord blood Hg concentration of 58μg/L are 0.3 and 0.2 μg/kg/day, respectively. For the 99th percentile, this is half the value previously estimated by the U.S. EPA. [ABSTRACT FROM AUTHOR]

Receptor for Advanced Glycation Endproducts (RAGE), a multiligand receptor in the immunoglobulin superfamily, functions as a signal-transducing cell surface acceptor for amyloid-beta peptide (Aß). In view of increased neuronal expression of RAGE in Alzheimer's disease, a murine model was developed to assess the impact of RAGE in an Aß-rich environment, employing transgenics (Tgs) with targeted neuronal overexpression of RAGE and mutant amyloid precursor protein (APP). Double Tgs (mutant APP (mAPP)/RAGE) displayed early abnormalities in spatial learning/memory, accompanied by altered activation of markers of synaptic plasticity and exaggerated neuropathologic findings, before such changes were found in mAPP mice. In contrast, Tg mice bearing a dominant-negative RAGE construct targeted to neurons crossed with mAPP animals displayed preservation of spatial learning/memory and diminished neuropathologic changes. These data indicate that RAGE is a cofactor for Aß-induced neuronal perturbation in a model of Alzheimer's-type pathology, and suggest its potential as a therapeutic target to ameliorate cellular dysfunction. [ABSTRACT FROM AUTHOR]

13C-detected experiments are still limited by their inherently lower sensitivity, as compared to the equivalent 1H-detected experiments. Improving the sensitivity of 13C detection methods remains a significant area of NMR research that may provide better means for studying large macromolecular systems by NMR. In this communication, we show that 13C-detected experiments are less sensitive to the salt concentration of the sample solution than 1H-detected experiments. In addition, acquisition can be started with anti-phase coherence, resulting in higher sensitivity due to the elimination of the final INEPT transfer step. [ABSTRACT FROM AUTHOR]

In 2000, the National Research Council (NRC), an arm of the National Academy of Sciences, released a report entitled, "Toxicological Effects of Methylmercury." The overall conclusion of that report was that, at levels of exposure in some fish- and marine mammal-consuming communities (including those in the Faroe Islands and New Zealand), subtle but significant adverse effects on neuropsychological development were occurring as a result of in utero exposure. Since the release of that report, there has been continuing discussion of the public health relevance of current levels of exposure to Methylmercury. Much of this discussion has been linked to the release of the most recent longitudinal update of the Seychelles Island study. It has recently been posited that these findings supercede those of the NRC committee, and that based on the Seychelles findings, there is little or no risk of adverse neurodevelopmental effects at current levels of exposure. In this commentary, members of the NRC committee address the conclusions from the NRC report in light of the recent Seychelles data. We conclude that no evidence has emerged since the publication of the NRC report that alters the findings of that report. [ABSTRACT FROM AUTHOR]