3-D Tracking and Visualization of Hundreds of Pt-Co Fuel Cell Nanocatalysts During Electrochemical Aging

We present an electron tomography method that allows for the identification of hundreds of electrocatalyst nanoparticles with one-to-one correspondence before and after electrochemical aging. This method allows us to track, in three-dimensions (3-D), the trajectories and morphologies of each Pt-Co nanocatalyst on a fuel cell carbon support. The use of atomic-scale electron energy loss spectroscopic imaging enables the correlation of performance degradation of the catalyst with changes in particle/inter-particle morphologies, particle-support interactions and the near-surface chemical composition. We found that, aging of the catalysts under normal fuel cell operating conditions (potential scans from +0.6 V to +1.0 V for 30,000 cycles) gives rise to coarsening of the nanoparticles, mainly through coalescence, which in turn leads to the loss of performance. The observed coalescence events were found to be the result of nanoparticle migration on the carbon support during potential cycling. This method provides detailed insights into how nanocatalyst degradation occurs in proton exchange membrane fuel cells (PEMFCs), and suggests that minimization of particle movement can potentially slow down the coarsening of the particles, and the corresponding performance degradation.Comment: Nano Letters, accepte

Evapotranspiration Rates of Riparian Forests, Platte River, Nebraska, 2002–06

Evapotranspiration (ET) in riparian areas is a poorly understood component of the regional water balance in the Platte River Basin, where competing demands have resulted in water shortages in the ground-water/surface-water system. From April 2002 through March 2006, the U.S. Geological Survey, Nebraska Platte River Cooperative Hydrology Study Group, and Central Platte Natural Resources District conducted a micrometeorological study of water and energy balances at two sites in central Nebraska near Odessa and Gothenburg to improve understanding of ET rates and factors affecting them in Platte River riparian forests. A secondary objective of the study was to constrain estimates of ground-water use by riparian vegetation to satisfy ET consumptive demands, a useful input to regional ground-water flow models. Both study sites are located on large islands within the Platte River characterized by a cottonwood-dominated forest canopy on primarily sandy alluvium. Although both sites are typical of riparian forests along the Platte River in Nebraska, the Odessa understory is dominated by deciduous shrubs, whereas the Gothenburg understory is dominated by eastern redcedars. Additionally, seasonal ground-water levels fluctuated more at Odessa than at Gothenburg. The study period of April 2002 through March 2006 encompassed precipitation conditions ranging from dry to wet. This study characterized the components of the water balance in the riparian zone of each site. ET was evaluated from eddy-covariance sensors installed on towers above the forest canopy at a height of 26.1 meters. Precipitation was measured both above and below the forest canopy. A series of sensors measured soil-moisture availability within the unsaturated zone in two different vertical profiles at each site. Changes in ground-water altitude were evaluated from piezometers. The areal footprint represented in the water balance extended up to 800 meters from each tower. During the study, ET was less variable than precipitation. Annual ET fluctuated about 7 percent from the 4-year mean, ranging from about 514 to 586 millimeters per year (551 on average) at the Odessa site and 535 to 616 millimeters per year (575 on average) at the Gothenburg site. Conversely, annual precipitation fluctuated by about 35 percent from the 4-year mean, ranging from 429 to 844 millimeters per year at Odessa and 359 to 791 millimeters per year at Gothenburg. Of this precipitation, 14 to 15 percent was intercepted by the forest canopy before it could infiltrate into the soil. For the 4-year period, annual ground-water recharge from the riparian measurement zone averaged 76 and 13 millimeters at Odessa and Gothenburg, respectively, to satisfy the water balance at each site. This indicates that, from an annual perspective, ground-water reductions caused by ET may be minimal. This effect varied somewhat and primarily was affected by fluctuations in precipitation. Ground-water discharge occurred during the driest study year (2002), whereas ground-water recharge occurred from 2003 to 2005. These results do not exclude ground water as an important source of water to riparian vegetation—especially to phreatophytes that have the capability of directly using water from the saturated zone—during periods of high ET in the summer, particularly during periods of lower than normal precipitation. However, the calculations indicate that, on an annual (or longer) net-flux basis, ground-water use by riparian forests is likely to be balanced by periods of recharge from excess precipitation at other times of the year. In contrast to more arid settings, where scientific literature indicates that ground water may supply a large fraction of the water used for ET by riparian vegetation, precipitation along the Platte River of Nebraska was great enough—and generally greater than ET—that most or all of the annual ET demand was satisfied by available precipitation. Crop coefficients developed for 15-day and monthly periods from the measured data predicted ET within 3.5 percent of actual annual ET; however, daily ET was underpredicted on days of increased ET and overpredicted on days of low ET. These crop coefficients can be used to extrapolate riparian-forest ET along the Platte River in conjunction with atmospheric data from other climate stations in central Nebraska. Regression models of simple and multiple-linear relations between explanatory variables and ET indicated that the relation of ET to environmental factors was different on days with precipitation than on dry days. At Odessa, ET was affected by vapor-pressure deficit, solar radiation, leaf-area index, and depth to water regardless of precipitation conditions, but was also affected by air temperature on days without precipitation, suggesting energy limitations on ET on days without precipitation. At Gothenburg, ET was always a function of vapor-pressure deficit, solar radiation, and leaf-area index, but, as with Odessa, air temperature also became important on days without precipitation. Despite depths to ground water of less than 2 meters and phreatophytic vegetation, measured ET was substantially less than potential ET (based on the modified Penman method), consistent with plant-stomatal regulation of ET in response to environmental and meteorological factors. Although annual ET rates generally were similar, the two sites exhibited different intraannual soil-moisture regimes that had a corresponding effect on ET and vegetation vigor. Smaller seasonal declines in ground-water levels and a lack of understory shrubs at the Gothenburg site as compared to the Odessa site may explain why Gothenburg ET was comparatively greater later in the summer and was not dependent on depth to water (as identified by the multiple-linear regression model). These differences also may explain why, during years of increased precipitation, ET rates increased at Odessa but not at Gothenburg

Evapotranspiration Rates of Riparian Forests, Platte River, Nebraska, 2002–06

Evapotranspiration (ET) in riparian areas is a poorly understood component of the regional water balance in the Platte River Basin, where competing demands have resulted in water shortages in the ground-water/surface-water system. From April 2002 through March 2006, the U.S. Geological Survey, Nebraska Platte River Cooperative Hydrology Study Group, and Central Platte Natural Resources District conducted a micrometeorological study of water and energy balances at two sites in central Nebraska near Odessa and Gothenburg to improve understanding of ET rates and factors affecting them in Platte River riparian forests. A secondary objective of the study was to constrain estimates of ground-water use by riparian vegetation to satisfy ET consumptive demands, a useful input to regional ground-water flow models. Both study sites are located on large islands within the Platte River characterized by a cottonwood-dominated forest canopy on primarily sandy alluvium. Although both sites are typical of riparian forests along the Platte River in Nebraska, the Odessa understory is dominated by deciduous shrubs, whereas the Gothenburg understory is dominated by eastern redcedars. Additionally, seasonal ground-water levels fluctuated more at Odessa than at Gothenburg. The study period of April 2002 through March 2006 encompassed precipitation conditions ranging from dry to wet. This study characterized the components of the water balance in the riparian zone of each site. ET was evaluated from eddy-covariance sensors installed on towers above the forest canopy at a height of 26.1 meters. Precipitation was measured both above and below the forest canopy. A series of sensors measured soil-moisture availability within the unsaturated zone in two different vertical profiles at each site. Changes in ground-water altitude were evaluated from piezometers. The areal footprint represented in the water balance extended up to 800 meters from each tower. During the study, ET was less variable than precipitation. Annual ET fluctuated about 7 percent from the 4-year mean, ranging from about 514 to 586 millimeters per year (551 on average) at the Odessa site and 535 to 616 millimeters per year (575 on average) at the Gothenburg site. Conversely, annual precipitation fluctuated by about 35 percent from the 4-year mean, ranging from 429 to 844 millimeters per year at Odessa and 359 to 791 millimeters per year at Gothenburg. Of this precipitation, 14 to 15 percent was intercepted by the forest canopy before it could infiltrate into the soil. For the 4-year period, annual ground-water recharge from the riparian measurement zone averaged 76 and 13 millimeters at Odessa and Gothenburg, respectively, to satisfy the water balance at each site. This indicates that, from an annual perspective, ground-water reductions caused by ET may be minimal. This effect varied somewhat and primarily was affected by fluctuations in precipitation. Ground-water discharge occurred during the driest study year (2002), whereas ground-water recharge occurred from 2003 to 2005. These results do not exclude ground water as an important source of water to riparian vegetation—especially to phreatophytes that have the capability of directly using water from the saturated zone—during periods of high ET in the summer, particularly during periods of lower than normal precipitation. However, the calculations indicate that, on an annual (or longer) net-flux basis, ground-water use by riparian forests is likely to be balanced by periods of recharge from excess precipitation at other times of the year. In contrast to more arid settings, where scientific literature indicates that ground water may supply a large fraction of the water used for ET by riparian vegetation, precipitation along the Platte River of Nebraska was great enough—and generally greater than ET—that most or all of the annual ET demand was satisfied by available precipitation. Crop coefficients developed for 15-day and monthly periods from the measured data predicted ET within 3.5 percent of actual annual ET; however, daily ET was underpredicted on days of increased ET and overpredicted on days of low ET. These crop coefficients can be used to extrapolate riparian-forest ET along the Platte River in conjunction with atmospheric data from other climate stations in central Nebraska. Regression models of simple and multiple-linear relations between explanatory variables and ET indicated that the relation of ET to environmental factors was different on days with precipitation than on dry days. At Odessa, ET was affected by vapor-pressure deficit, solar radiation, leaf-area index, and depth to water regardless of precipitation conditions, but was also affected by air temperature on days without precipitation, suggesting energy limitations on ET on days without precipitation. At Gothenburg, ET was always a function of vapor-pressure deficit, solar radiation, and leaf-area index, but, as with Odessa, air temperature also became important on days without precipitation. Despite depths to ground water of less than 2 meters and phreatophytic vegetation, measured ET was substantially less than potential ET (based on the modified Penman method), consistent with plant-stomatal regulation of ET in response to environmental and meteorological factors. Although annual ET rates generally were similar, the two sites exhibited different intraannual soil-moisture regimes that had a corresponding effect on ET and vegetation vigor. Smaller seasonal declines in ground-water levels and a lack of understory shrubs at the Gothenburg site as compared to the Odessa site may explain why Gothenburg ET was comparatively greater later in the summer and was not dependent on depth to water (as identified by the multiple-linear regression model). These differences also may explain why, during years of increased precipitation, ET rates increased at Odessa but not at Gothenburg

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

Of Mice and Measures : A Project to Improve How We Advance Duchenne Muscular Dystrophy Therapies to the Clinic.

A new line of dystrophic mdx mice on the DBA/2J (D2) background has emerged as a candidate to study the efficacy of therapeutic approaches for Duchenne muscular dystrophy (DMD). These mice harbor genetic polymorphisms that appear to increase the severity of the dystropathology, with disease modifiers that also occur in DMD patients, making them attractive for efficacy studies and drug development. This workshop aimed at collecting and consolidating available data on the pathological features and the natural history of these new D2/mdx mice, for comparison with classic mdx mice and controls, and to identify gaps in information and their potential value. The overall aim is to establish guidance on how to best use the D2/mdx mouse model in preclinical studies

SlowMo, a digital therapy targeting reasoning in paranoia, versus treatment as usual in the treatment of people who fear harm from others: study protocol for a randomised controlled trial

Background: Paranoia is one of the most common symptoms of schizophrenia-spectrum disorders, and is associated with significant distress and disruption to the person’s life. Developing more effective and accessible psychological interventions for paranoia is a clinical priority. Our research team has approached this challenge in two main ways: firstly, by adopting an interventionist causal approach to increase effectiveness and secondly, by incorporating user-centred inclusive design methods to enhance accessibility and usability. Our resultant new digital intervention, SlowMo, intensively targets a reasoning style associated with paranoia, fast thinking, characterised by jumping to conclusions and belief inflexibility. It consists of an easy-to-use, enjoyable and memorable digital interface. An interactive web-based app facilitates delivery of face-to-face meetings which is then synchronised with an innovative mobile app for use in daily life. Methods/Design: We aim to test the clinical efficacy of SlowMo over 24 weeks to determine the mechanisms through which it reduces paranoia, and to identify participant characteristics that moderate its effectiveness. In a parallel-group randomised controlled trial, with 1:1 allocation, 360 participants with distressing persecutory beliefs will be independently randomised to receive either the SlowMo intervention added to treatment as usual (TAU) or TAU, using randomly varying permuted blocks, stratified by paranoia severity and site. Research workers will be blind to therapy allocation. The primary outcome is paranoia severity over 24 weeks; our hypothesised mechanism of change is reasoning; moderators include negative symptoms and working memory; and secondary outcomes include wellbeing, quality of life, and service use. The accessibility, usability and acceptability of the digital platform will be assessed. Discussion: SlowMo has been developed as the first blended digital therapy to target fears of harm from others through an inclusive design approach. In addition to testing its efficacy, this trial will add to our understanding of psychological mechanisms in paranoia. The study will examine the usability and adherence of a novel digital therapy, including an app for self-management, in a large sample of people affected by severe mental health difficulties

Variation in Molybdenum Content Across Broadly Distributed Populations of Arabidopsis thaliana Is Controlled by a Mitochondrial Molybdenum Transporter (MOT1)

Molybdenum (Mo) is an essential micronutrient for plants, serving as a cofactor for enzymes involved in nitrate assimilation, sulfite detoxification, abscisic acid biosynthesis, and purine degradation. Here we show that natural variation in shoot Mo content across 92 Arabidopsis thaliana accessions is controlled by variation in a mitochondrially localized transporter (Molybdenum Transporter 1 - MOT1) that belongs to the sulfate transporter superfamily. A deletion in the MOT1 promoter is strongly associated with low shoot Mo, occurring in seven of the accessions with the lowest shoot content of Mo. Consistent with the low Mo phenotype, MOT1 expression in low Mo accessions is reduced. Reciprocal grafting experiments demonstrate that the roots of Ler-0 are responsible for the low Mo accumulation in shoot, and GUS localization demonstrates that MOT1 is expressed strongly in the roots. MOT1 contains an N-terminal mitochondrial targeting sequence and expression of MOT1 tagged with GFP in protoplasts and transgenic plants, establishing the mitochondrial localization of this protein. Furthermore, expression of MOT1 specifically enhances Mo accumulation in yeast by 5-fold, consistent with MOT1 functioning as a molybdate transporter. This work provides the first molecular insight into the processes that regulate Mo accumulation in plants and shows that novel loci can be detected by association mapping

Biodiversity of Mineral Nutrient and Trace Element Accumulation in Arabidopsis thaliana

In order to grow on soils that vary widely in chemical composition, plants have evolved mechanisms for regulating the elemental composition of their tissues to balance the mineral nutrient and trace element bioavailability in the soil with the requirements of the plant for growth and development. The biodiversity that exists within a species can be utilized to investigate how regulatory mechanisms of individual elements interact and to identify genes important for these processes. We analyzed the elemental composition (ionome) of a set of 96 wild accessions of the genetic model plant Arabidopsis thaliana grown in hydroponic culture and soil using inductively coupled plasma mass spectrometry (ICP-MS). The concentrations of 17–19 elements were analyzed in roots and leaves from plants grown hydroponically, and leaves and seeds from plants grown in artificial soil. Significant genetic effects were detected for almost every element analyzed. We observed very few correlations between the elemental composition of the leaves and either the roots or seeds. There were many pairs of elements that were significantly correlated with each other within a tissue, but almost none of these pairs were consistently correlated across tissues and growth conditions, a phenomenon observed in several previous studies. These results suggest that the ionome of a plant tissue is variable, yet tightly controlled by genes and gene×environment interactions. The dataset provides a valuable resource for mapping studies to identify genes regulating elemental accumulation. All of the ionomic data is available at www.ionomicshub.org

Rudra Interrupts Receptor Signaling Complexes to Negatively Regulate the IMD Pathway

Insects rely primarily on innate immune responses to fight pathogens. In Drosophila, antimicrobial peptides are key contributors to host defense. Antimicrobial peptide gene expression is regulated by the IMD and Toll pathways. Bacterial peptidoglycans trigger these pathways, through recognition by peptidoglycan recognition proteins (PGRPs). DAP-type peptidoglycan triggers the IMD pathway via PGRP-LC and PGRP-LE, while lysine-type peptidoglycan is an agonist for the Toll pathway through PGRP-SA and PGRP-SD. Recent work has shown that the intensity and duration of the immune responses initiating with these receptors is tightly regulated at multiple levels, by a series of negative regulators. Through two-hybrid screening with PGRP-LC, we identified Rudra, a new regulator of the IMD pathway, and demonstrate that it is a critical feedback inhibitor of peptidoglycan receptor signaling. Following stimulation of the IMD pathway, rudra expression was rapidly induced. In cells, RNAi targeting of rudra caused a marked up-regulation of antimicrobial peptide gene expression. rudra mutant flies also hyper-activated antimicrobial peptide genes and were more resistant to infection with the insect pathogen Erwinia carotovora carotovora. Molecularly, Rudra was found to bind and interfere with both PGRP-LC and PGRP-LE, disrupting their signaling complex. These results show that Rudra is a critical component in a negative feedback loop, whereby immune-induced gene expression rapidly produces a potent inhibitor that binds and inhibits pattern recognition receptors