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Climate change is predicted to increase the frequency and impact of plant invasions, creating a need for new control strategies as part of mitigation planning. The complex interactions between invasive plants and biocontrol agents have created distinct policy and management challenges, including the effectiveness and risk assessment of biocontrol under different climate change scenarios. In this brief review, we synthesize recent studies describing the potential ecological and evolutionary outcomes for biocontrol agents/candidates for plant invaders under climate change. We also discuss potential methodologies that can be used as a framework for predicting ecological and evolutionary responses of plant-natural enemy interactions under climate change, and for refining our understanding of the efficacy and risk of using biocontrol on invasive plants.

A scanning transmission electron diffraction method is developed for use in the scanning electron microscope to perform orientational characterization of 2D materials. The method can generate orientation maps of monolayer graphene over a field of view up to ≈ 50 μ m in just a few minutes and can distinguish twisted bilayers from aligned bilayers. This method holds promise to bring electron-diffraction-based orientation measurements of 2D materials to a broader audience.

An organism’s capacity to cope with stressful experiences is dependent on its ability to appropriately engage central and peripheral systems, such as the hypothalamic-pituitary-adrenal (HPA) axis, to adapt to changing environmental demands. The HPA axis is a primary neuroendocrine mediator of neural and behavioral responses to stress, and dysfunction of this system is linked to increased risk for developing mental health disorders such as depression, anxiety, and post-traumatic stress disorder. However, the mechanisms by which dysregulated HPA function results in abnormal behavioral responses to stress are poorly understood. Here, we tested how corticosterone (CORT)-induced HPA axis disruption affects behavioral responses to stress in male C57BL/6 N mice, and probed correlates of these behaviors in the brain. We show that chronic HPA disruption blunts acute stress-induced grooming and rearing behaviors in the open field test, effects which were accompanied by decreased FOS immunoreactivity in the paraventricular nucleus of the hypothalamus (PVH) and paraventricular nucleus of the thalamus (PVT). Blockade of CORT secretion with metyrapone injection prior to acute stress did not recapitulate the effects of chronic HPA disruption on open field behavior, and acute CORT replacement did not rescue normal behavioral stress responses following chronic HPA disruption. This suggests that under acute conditions, CORT is not necessary for these responses normally, nor sufficient to rescue the deficits of chronic HPA dysregulation. Together, these findings support the hypothesis that chronic HPA dysregulation causes adaptation in stress-related brain circuits and demonstrate that these changes can influence an organism’s behavioral response to stress exposure.

Shifts in forest tree phenology are one of the most important and conspicuous plant responses to climate variability. However, systematically documenting changes in phenology of individual trees across large areas at high temporal frequency is often prohibitively labor- and resource-intensive. Here we present a new method that uses accelerometers to overcome challenges of measuring high-frequency tree phenology in the field. Accelerometers are small, portable devices that can be attached to trees to record movement due to forcing by wind. Time series analyses of tree movement data recorded by accelerometers can yield an approximation of tree mass. Because leaf emergence and leaf drop alter aboveground tree mass, these phenological events are expected to be detectable from accelerometer data. To test how well accelerometers can be used to measure phenological dates, we deployed 20 accelerometers on balsam poplar (Populus balsamifera) trees across a variety of sites during the 2016 growing season and assessed how well phenology derived from accelerometers matched visual observation of phenology recorded by citizen scientists. We found that accelerometer measurements fit the theoretical expectation for the seasonal change in tree mass associated with leaf phenology; specifically, an increase in tree mass in the spring, and a decline in the autumn. Furthermore, we found that accelerometer-derived phenology matched visual observations for leaf emergence, with a strong correlation between the dates of first observed full leaves and accelerometer-derived phenology (r = 0.82, p

IL-7 receptor signaling is essential for the generation and maintenance of conventional T cells. Immunosuppressive Foxp3+ Treg cells, however, express uniquely low amounts of the IL-7-proprietary IL-7Rα so that they are impaired in IL-7 signaling. Because Treg cells depend on IL-2, the loss of IL-7Rα has been considered irrelevant for Treg cells. In contrast, here, we report that IL-7Rα downregulation is necessary to maximize IL-2R signaling. While IL-7Rα overexpression promoted IL-7 signaling, unexpectedly, IL-2 signaling was suppressed in the same cells. Mechanistically, we found that γc, which is a receptor subunit shared by IL-7R and IL-2R, directly binds and pre-associates with IL-7Rα, thus limiting its availability for IL-2R binding. Consequently, overexpression of signaling-deficient, tailless IL-7Rα proteins inhibited IL-2R signaling, demonstrating that IL-7Rα sequesters γc and suppresses IL-2R signaling by extracellular interactions. Collectively, these results reveal a previously unappreciated regulatory mechanism of IL-2 receptor signaling that is governed by IL-7Rα abundance.

Anhedonia (i.e., diminished capacity to experience pleasure) has traditionally been viewed as a core symptom of schizophrenia (SZ). However, modern laboratory-based studies suggest that this definition may be incorrect, as hedonic capacity may be intact. Alternative conceptualizations have proposed that anhedonia may reflect an impairment in generating mental representations of affective value that are needed to guide decision-making and initiate motivated behavior. The current study evaluated this hypothesis in 42 outpatients with SZ and 19 healthy controls (CN) who completed two tasks: (a) an emotional experience task that required them to indicate how positive, negative, and calm/excited they felt in response to a single emotional or neutral photograph; (b) a relative value judgment task where they selected which of 2 photographs they preferred. Results indicated that SZ and CN reported similar levels of positive emotion and arousal in response to emotional and neutral stimuli; however, SZ reported higher negative affect for neutral and pleasant stimuli than CN. In the relative value judgment task, CN displayed clear preference for stimuli differing in valence; however, SZ showed less distinct preferences for positive over neutral stimuli. Findings suggest that although in-the-moment experiences of positive emotion to singular stimuli may be intact in SZ, the ability to make relative value judgments that are needed to guide decision-making is impaired. Original conceptualizations of anhedonia as a diminished capacity for pleasure in SZ may be inaccurate; anhedonia may more accurately reflect a deficit in relative value judgment that results from impaired value representation.

SUMMARY Fetal globin genes are transcriptionally silenced during embryogenesis through hemoglobin switching. Strategies to derepress fetal globin expression in the adult could alleviate symptoms in sickle cell disease and β-thalassemia. We identified a zinc-finger protein, pogo transposable element with zinc-finger domain (POGZ), expressed in hematopoietic progenitor cells. Targeted deletion of Pogz in adult hematopoietic cells in vivo results in persistence of embryonic β-like globin expression without affecting erythroid development. POGZ binds to the Bcl11a promoter and erythroid-specific intragenic regulatory regions. Pogz+/− mice show elevated embryonic β-like globin expression, suggesting that partial reduction of Pogz expression results in persistence of embryonic β-like globin expression. Knockdown of POGZ in primary human CD34+ progenitor cell-derived erythroblasts reduces BCL11A expression, a known repressor of embryonic β-like globin expression, and increases fetal hemoglobin expression. These findings are significant, since new therapeutic targets and strategies are needed to treat β-globin disorders., In Brief Gudmundsdottir et al. show that POGZ represses embryonic globin gene expression in mouse and human erythroid cells, in part by regulating Bcl11a expression in vitro and in vivo. The molecular pathways regulated by POGZ may represent potential therapeutic targets to increase fetal globin expression in patients with sickle cell disease and β-thalassemia., Graphical Abstract

In this paper, a simulation tool was employed to identify and appropriately incorporate differences between MiniColumns and benchtop column systems. It was first demonstrated that including multi-step gradients and fraction collection into the simulations resulted in improved agreement between simulated and experimental linear gradient profiles as well as calculated first moments in the MiniColumn experiments. Step elution experiments of binary mixtures (a monoclonal antibody and one of three model proteins) were then carried out to examine comparability of the MiniColumns to the benchtop system. Although the peak shapes were qualitatively similar, peak elution began earlier in the MiniColumn system while improved separation was observed between overlapping peaks using the benchtop format. Simulations were then carried out to demonstrate that increased dispersion of the eluent breakthrough in the benchtop system could readily explain these observed differences. Importantly, by incorporating these system differences into the simulations, we were able to predict benchtop step elution performance using the parameters solely obtained from the MiniColumns. The findings presented in this paper illustrate that the appropriate consideration of system differences can facilitate the implementation of miniature chromatography columns as scale-down models for bioprocess development.

Transmission electron backscatter diffraction (t-EBSD) has become a routine technique for crystal orientation mapping when ultrahigh resolution is needed and has demonstrated advantages in the characterization of nanoscale and micron-sized samples (Babinsky et al., 2015). In this work, we use experimental measurements and simulations to compare the resolution of the transmission and conventional reflection EBSD techniques across a range of sample volumes and characterization conditions. Monte Carlo simulations of electron trajectories provide the opportunity to estimate beam size and effective resolution, as well as electron flux, as a function of sample thickness or incident beam energy in t-EBSD. Increasing incident beam energy is shown to negatively impact beam diameter in some cases, and the effect of thinning a sample for conventional EBSD is shown to improve characterization resolution but dramatically decrease the number of high-loss electrons backscattered to the detector. In addition to considering spatial resolution when implementing EBSD techniques, it is found that maintaining a high yield of diffracted electrons to the detector is also of critical importance, which is supported by experimental results. Consequently, this work provides key insights into the nature of electron scattering and probe volume for the practical implementation of both transmission and reflection EBSD techniques.

An annular dark field (ADF) detector was placed beneath a specimen in a field emission scanning electron microscope operated at 30kV to calibrate detector response to incident beam current, and to create transmission images of gold nanoparticles on silicon nitride (SiN) substrates of various thicknesses. Based on the linear response of the ADF detector diodes to beam current, we developed a method that allowed for direct determination of the percentage of that beam current forward scattered to the ADF detector from the sample, i.e. the transmitted electron (TE) yield. Collection angles for the ADF detector region were defined using a masking aperture above the detector and were systematically varied by changing the sample to detector distance. We found the contrast of the nanoparticles, relative to the SiN substrate, decreased monotonically with decreasing inner exclusion angle and increasing substrate thickness. We also performed Monte Carlo electron scattering simulations, which showed quantitative agreement with experimental contrast associated with the nanoparticles. Together, the experiments and Monte Carlo simulations revealed that the decrease in contrast with decreasing inner exclusion angle was due to a rapid increase in the TE yield of the low atomic number substrate. Nanoparticles imaged at low inner exclusion angles (150mrad) and on thick substrates (50nm) showed low image contrast in their centers surrounded by a bright high-contrast halo on their edges. This complex image contrast was predicted by Monte Carlo simulations, which we interpreted in terms of mixing of the nominally bright field (BF) and ADF electron signals. Our systematic investigation of inner exclusion angle and substrate thickness effects on ADF t-SEM imaging provides fundamental understanding of the contrast mechanisms for image formation, which in turn suggest practical limitations and optimal imaging conditions for different substrate thicknesses.

NASA's Orbiting Carbon Observatory-3 (OCO-3) was installed on the International Space Station (ISS) on 10 May 2019. OCO-3 combines the flight spare spectrometer from the Orbiting Carbon Observatory-2 (OCO-2) mission, which has been in operation since 2014, with a new Pointing Mirror Assembly (PMA) that facilitates observations of non-nadir targets from the nadir-oriented ISS platform. The PMA is a new feature of OCO-3, which is being used to collect data in all science modes, including nadir (ND), sun-glint (GL), target (TG), and the new snapshot area mapping (SAM) mode. This work provides an initial assessment of the OCO-3 instrument and algorithm performance, highlighting results from the first 8 months of operations spanning August 2019 through March 2020. During the In-Orbit Checkout (IOC) phase, critical systems such as power and cooling were verified, after which the OCO-3 spectrometer and PMA were subjected to a series of rigorous tests. First light of the OCO-3 spectrometer was on 26 June 2019, with full science operations beginning on 6 August 2019. The OCO-3 spectrometer on-orbit performance is consistent with that seen during preflight testing. Signal to noise ratios are in the expected range needed for high quality retrievals of the column-averaged carbon dioxide (CO2) dry-air mole fraction (XCO2) and solar-induced chlorophyll fluorescence (SIF), which will be used to help quantify and constrain the global carbon cycle. The first public release of OCO-3 Level 2 (L2) data products, called “vEarly”, is being distributed by NASA's Goddard Earth Sciences Data and Information Services Center (GES DISC). The intent of the vEarly product is to evaluate early mission performance, facilitate comparisons with OCO-2 products, and identify key areas to improve for the next data release. The vEarly XCO2 exhibits a root-mean-squared-error (RMSE) of ≃ 1, 1, 2 ppm versus a truth proxy for nadir-land, TG&SAM, and glint-water observations, respectively. The vEarly SIF shows a correlation with OCO-2 measurements of >0.9 for highly coincident soundings. Overall, the Level 2 SIF and XCO2 products look very promising, with performance comparable to OCO-2. A follow-on version of the OCO-3 L2 product containing a number of refinements, e.g., instrument calibration, pointing accuracy, and retrieval algorithm tuning, is anticipated by early in 2021.

There are numerous cost-effective applications for geosynthetics on low-volume roads, yet geosynthetic materials use on these roads is typically underutilized. The USDA Forest Service has been using geosynthetics on its low-volume roads for the past 40 years in applications of separation, reinforcement, drainage, filtration, and others. The objective of this paper is to document many of these uses on low-volume forest roads, both traditional and unique, and discuss the many cost-effective advantages of geosynthetic use. Uses in low-volume road applications are similar to those used in many highway projects, and have many of the same benefits and cost savings, yet utilization is variable and inconsistent. In many developing countries, engineers and technicians designing rural roads have barely heard of geosynthetic materials, much less taken advantage of their benefits. Low volume roads make up roughly two thirds of all the roads worldwide, or roughly 30 million kilometers of roads, yet they do not receive the attention and appropriate technologies deserving of such a major amount of infrastructure. Significant cost savings and improvements in design and ultimately roadway performance can be realized with the increased use of geosynthetics in underdrains, for subgrade reinforcement, in geosynthetically reinforced retaining structures, and in improved erosion control. Materials used include geotextiles, geogrids, geocells, geofoam, netting, and other geosynthetics.

This work presents recent advances in transmission scanning electron microscopy (t-SEM) imaging control capabilities. A modular aperture system and a cantilever-style sample holder that enable comprehensive angular selectivity of forward-scattered electrons are described. When combined with a commercially available solid-state transmission detector having only basic bright-field and dark-field imaging capabilities, the advances described here enable numerous transmission imaging modes. Several examples are provided that demonstrate how contrast arising from diffraction to mass-thickness can be obtained. Unanticipated image contrast at some imaging conditions is also observed and addressed.

Summary IL-7 receptor signaling is essential for the generation and maintenance of conventional T cells. Immunosuppressive Foxp3+ Treg cells, however, express uniquely low amounts of the IL-7-proprietary IL-7Rα so that they are impaired in IL-7 signaling. Because Treg cells depend on IL-2, the loss of IL-7Rα has been considered irrelevant for Treg cells. In contrast, here, we report that IL-7Rα downregulation is necessary to maximize IL-2R signaling. Although IL-7Rα overexpression promoted IL-7 signaling, unexpectedly, IL-2 signaling was suppressed in the same cells. Mechanistically, we found that γc, which is a receptor subunit shared by IL-7R and IL-2R, directly binds and pre-associates with IL-7Rα, thus limiting its availability for IL-2R binding. Consequently, overexpression of signaling-deficient, tailless IL-7Rα proteins inhibited IL-2R signaling, demonstrating that IL-7Rα sequesters γc and suppresses IL-2R signaling by extracellular interactions. Collectively, these results reveal a previously unappreciated regulatory mechanism of IL-2 receptor signaling that is governed by IL-7Rα abundance., Graphical Abstract, Highlights • The availability of γc is limited, so that IL-7Rα and IL-2Rβ compete for γc to signal • IL-7Rα has high affinity for γc, and it outcompetes IL-2Rβ for binding to γc • Foxp3+ Treg cells express low amounts of IL-7Rα, which frees γc for IL-2Rβ binding • Forced IL-7Rα expression sequesters γc and impairs IL-2R signaling in Treg cells, Molecular Biology; Immunology

Summary: Investigating mechanisms that regulate endothelial cell (EC) growth and survival is important for understanding EC homeostasis and how ECs maintain stem cell niches. We report here that targeted loss of Id genes in adult ECs results in dilated, leaky sinusoids and a pro-inflammatory state that increases in severity over time. Disruption in sinusoidal integrity leads to increased hematopoietic stem cell (HSC) proliferation, differentiation, migration, and exhaustion. Mechanistically, sinusoidal ECs (SECs) show increased apoptosis because of reduced Bcl2-family gene expression following Id gene ablation. Furthermore, Id1−/−Id3−/− SECs and upstream type H vessels show increased expression of cyclin-dependent kinase inhibitors p21 and p27 and impaired ability to proliferate, which is rescued by reducing E2-2 expression. Id1−/−Id3−/− mice do not survive sublethal irradiation because of impaired vessel regeneration and hematopoietic failure. Thus, Id genes are required for the survival and regeneration of BM SECs during homeostasis and stress to maintain HSC development. : Gadomski et al. show that Id genes are critical regulators of bone marrow endothelial cell proliferation and survival. Selective loss of Id genes in endothelial cells promotes vessel dilation, apoptosis, and increased permeability, leading to the functional decline of hematopoietic stem cells under steady-state and stress conditions. Keywords: endothelial cells, ID proteins, hematopoietic stem cells, hematopoietic microenvironment, instructive niche, transcription factors, tissue regeneration, progenitor cells, proliferation, bone marrow

Lymphoid tissue inducer (LTi) cells are regarded as a subset of innate lymphoid cells (ILCs). However, these cells are not derived from the ILC common progenitor, which generates other ILC subsets and is defined by the expression of the transcription factor PLZF. Here, we examined transcription factor(s) determining the fate of LTi progenitors versus non-LTi ILC progenitors. Conditional deletion of Gata3 resulted in the loss of PLZF+ non-LTi progenitors but not the LTi progenitors that expressed the transcription factor RORγt. Consistently, PLZF+ non-LTi progenitors expressed high amounts of GATA3, whereas GATA3 expression was low in RORγt+ LTi progenitors. The generation of both progenitors required the transcriptional regulator Id2, which defines the common helper-like innate lymphoid progenitor (ChILP), but not cytokine signaling. Nevertheless, low GATA3 expression was necessary for the generation of functionally mature LTi cells. Thus, differential expression of GATA3 determines the fates and functions of distinct ILC progenitors.

In this paper, a comparison between experimental chromatography data and column simulations is carried out to determine the efficacy of using miniaturized chromatography columns (MiniColumns) for both column modeling parameter estimation and process development. Normalization of the data with respect to column volumes along with appropriate translations to account for system differences is shown to result in comparability of the experimental data for the MiniColumn and benchtop systems. A parameter estimation protocol is then employed to determine the linear steric mass-action (SMA) isotherm and lumped mass transport parameters for two cation exchange resins. The models are then validated and simulations using different parameter sets from the MiniColumn and benchtop systems are shown to result in similar predicted chromatography profiles and calculated retention volumes. The parameters generated from the MiniColumn system are demonstrated to be well suited for predicting experimental data from the benchtop system. These simulation results, the ability to operate MiniColumns in parallel, and the significantly lower material requirements per experiment support an industry trend toward increased usage of miniaturized chromatography columns as a scale-down model for process development.

Objective Defective glucose uptake in adipocytes leads to impaired metabolic homeostasis and insulin resistance, hallmarks of type 2 diabetes. Extracellular ATP-derived nucleotides and nucleosides are important regulators of adipocyte function, but the pathway for controlled ATP release from adipocytes is unknown. Here, we investigated whether Pannexin 1 (Panx1) channels control ATP release from adipocytes and contribute to metabolic homeostasis. Methods We assessed Panx1 functionality in cultured 3T3-L1 adipocytes and in adipocytes isolated from murine white adipose tissue by measuring ATP release in response to known activators of Panx1 channels. Glucose uptake in cultured 3T3-L1 adipocytes was measured in the presence of Panx1 pharmacologic inhibitors and in adipocytes isolated from white adipose tissue from wildtype (WT) or adipocyte-specific Panx1 knockout (AdipPanx1 KO) mice generated in our laboratory. We performed in vivo glucose uptake studies in chow fed WT and AdipPanx1 KO mice and assessed insulin resistance in WT and AdipPanx1 KO mice fed a high fat diet for 12 weeks. Panx1 channel function was assessed in response to insulin by performing electrophysiologic recordings in a heterologous expression system. Finally, we measured Panx1 mRNA in human visceral adipose tissue samples by qRT-PCR and compared expression levels with glucose levels and HOMA-IR measurements in patients. Results Our data show that adipocytes express functional Pannexin 1 (Panx1) channels that can be activated to release ATP. Pharmacologic inhibition or selective genetic deletion of Panx1 from adipocytes decreased insulin-induced glucose uptake in vitro and in vivo and exacerbated diet-induced insulin resistance in mice. Further, we identify insulin as a novel activator of Panx1 channels. In obese humans Panx1 expression in adipose tissue is increased and correlates with the degree of insulin resistance. Conclusions We show that Panx1 channel activity regulates insulin-stimulated glucose uptake in adipocytes and thus contributes to control of metabolic homeostasis., Graphical abstract, Highlights • Adipocytes express Pannexin 1 channels that can be activated to release ATP. • Inhibition of Pannexin 1 decreased insulin-induced glucose uptake in adipocytes. • Adipocyte Pannexin 1 knockout mice are more insulin resistant on high fat diet. • We identify insulin as a novel activator of Pannexin 1 channels. • Pannexin 1 expression in human adipose tissue correlates with insulin resistance.

A principal data product from MESSENGER’s primary orbital mission at Mercury is a global multispectral map in eight visible to near-infrared colors, at an average pixel scale of 1 km, acquired by the Mercury Dual Imaging System. The constituent images have been calibrated, photometrically corrected to a standard geometry, and map projected. Global analysis reveals no spectral units not seen during MESSENGER’s Mercury flybys and supports previous conclusions that most spectral variation is related to changes in spectral slope and reflectance between spectral end-member high-reflectance red plains (HRP) and low-reflectance material (LRM). Comparison of color properties of plains units mapped on the basis of morphology shows that the two largest unambiguously volcanic smooth plains deposits (the interior plains of Caloris and the northern plains) are close to HRP end members and have average color properties distinct from those of most other smooth plains and intercrater plains. In contrast, smaller deposits of smooth plains are nearly indistinguishable from intercrater plains on the basis of their range of color properties, consistent with the interpretation that intercrater plains are older equivalents of smooth plains. LRM having nearly the same reflectance is exposed in crater and basin ejecta of all ages, suggesting impact excavation from depth of material that is intrinsically dark or darkens very rapidly, rather than gradual darkening of exposed material purely by space weathering. A global search reveals no definitive absorptions attributable to Fe 2+ -containing silicates or to sulfides over regions 20 km or more in horizontal extent, consistent with results from MESSENGER’s Mercury Atmospheric and Surface Composition Spectrometer. The only absorption-like feature identified is broad upward curvature of the spectrum centered near 600 nm wavelength. The feature is strongest in freshly exposed LRM and weak or absent in older exposures of LRM. We modeled spectra of LRM as intimate mixtures of HRP with candidate low-reflectance phases having a similar 600-nm spectral feature, under the assumption that the grain size is 1 μm or larger. Sulfides measured to date in the laboratory and coarse-grained iron are both too bright to produce LRM from HRP. Ilmenite is sufficiently dark but would require Ti abundances too high to be consistent with MESSENGER X-Ray Spectrometer measurements. Three phases or mixtures of phases that could be responsible for the low reflectance of LRM are consistent with our analyses. Graphite, in amounts consistent with upper limits from the Gamma-Ray Spectrometer, may be consistent with geochemical models of Mercury’s differentiation calling for a graphite-enriched primary flotation crust from an early magma ocean and impact mixing of that early crust before or during the late heavy bombardment (LHB) into material underlying the volcanic plains. The grain size of preexisting iron or iron sulfide could have been altered to a mix of nanophase and microphase grains by shock during those impacts, lowering reflectance. Alternatively, iron-bearing phases and carbon in a late-accreting carbonaceous veneer may have been stirred into the lower crust or upper mantle. Decoupling of variations in color from abundances of major elements probably results from the very low content and variation of Fe 2+ in crustal silicates, such that reflectance is controlled instead by one or more minor opaque phases and the extent of space weathering.

As researchers strive to identify the components of effective preparation for study abroad, it is also critical to investigate the beliefs and expectations about intercultural adjustment that students bring to these interventions. A questionnaire assessed the structure and correlates of 149 U.S. undergraduate students’ lay theories of culture shock. Findings indicated that students tended to attribute culture shock to differences in the external environment, such as language, communication, and surroundings, rather than to internal affective or cognitive factors, such as poor stress management, identity confusion, or prejudice. The tendency to attribute culture shock to internal causes was greater for those with higher levels of cultural competence, whereas low travel experience and interest in foreign language learning predicted the tendency to attribute culture shock to external causes. These results are discussed in terms of implications for sojourner adjustment and intercultural training.

Firearm serial numbers are a critical identifying mark, and restoration of destroyed serial numbers is often crucial for prosecution of a criminal case. A method is presented utilizing electron backscatter diffraction (EBSD) in the scanning electron microscope (SEM) which allows for clear visualization of die-stamped imprints which have been completely polished away. Evidence of the stamp can be observed to a depth of approximately 760μm below the surface. With further development, the described method is capable of reconstructing an 8 character serial number in approximately 1h.

Lower endogenous oxytocin levels have been associated with impaired social cognition in schizophrenia, particularly facial affect identification. Little is known about the relationship between oxytocin and other forms of emotion perception. In the current study, 41 individuals with schizophrenia (SZ) and 22 demographically matched healthy controls (CN) completed a forced-choice affective body expression classification task. Stimuli included dynamic videos of male and female actors portraying 4 discrete emotions: happiness, sadness, anger, and neutral. Plasma oxytocin levels were determined via radioimmunoassay. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ were also less accurate at identifying expressions of happiness and sadness; however, there were no group differences for anger or neutral stimuli. A group x sex interaction was also present, such that female CN were more accurate than male CN, whereas male SZ were more accurate than female SZ. Higher endogenous oxytocin levels were associated with better total recognition in both SZ and CN; this association was specific to females in SZ. Findings indicate that sex plays an important role in identifying emotional expressions in body gestures in SZ, and that individual differences in endogenous oxytocin predict emotion perception accuracy.

Electrical failure of 14 American Wire Gauge nonmetallic-sheathed cable, which is used widely in residential electric circuits in the United States, was examined in a range of high temperature environments. Slow heating rates were maintained in these environments to ensure that the heat transfer inside the cable was not a significant factor in the failure process. The experiments were performed in non-energized configuration (insulation electrical resistance was measured), energized with a nominal voltage of 120 V of alternating current and no load, and energized and loaded configurations. In the case of energized experiments, the main parameter that was determined was the time to cable failure. This time was found to be highly reproducible and strongly dependent on the cable temperature. Individual cable insulation components were also examined in a range of experiments including thermogravimetric analysis to gain insight into the mechanism of the failure process. It was determined that the time to cable failure can be quantitatively linked to a particular insulation component reaching a critical degree of thermal decomposition. The use of this criterion within the framework of a thermal degradation model, which was parameterized based on anaerobic thermogravimetric analysis, produced reasonably accurate predictions of the times to failure for a range of energized cable tests.

The study of cellular signaling remains a significant challenge for translational and clinical research. In particular, robust and accurate methods for quantitative phosphoproteomics in tissues and tumors represent significant hurdles for such efforts. In the present work, we design, implement and validate a method for single-stage phosphopeptide enrichment and stable isotope chemical tagging, or SPECHT, that enables the use of iTRAQ, TMT and/or reductive dimethyl-labeling strategies to be applied to phosphoproteomics experiments performed on primary tissue. We develop and validate our approach using reductive dimethyl-labeling and HeLa cells in culture, and find these results indistinguishable from data generated from more traditional SILAC-labeled HeLa cells mixed at the cell level. We apply the SPECHT approach to the quantitative analysis of insulin signaling in a murine myotube cell line and muscle tissue, identify known as well as new phosphorylation events, and validate these phosphorylation sites using phospho-specific antibodies. Taken together, our work validates chemical tagging post-single-stage phosphoenrichment as a general strategy for studying cellular signaling in primary tissues.Through the use of a quantitatively reproducible, proteome-wide phosphopeptide enrichment strategy, we demonstrated the feasibility of post-phosphopeptide purification chemical labeling and tagging as an enabling approach for quantitative phosphoproteomics of primary tissues. Using reductive dimethyl labeling as a generalized chemical tagging strategy, we compared the performance of post-phosphopeptide purification chemical tagging to the well established community standard, SILAC, in insulin-stimulated tissue culture cells. We then extended our method to the analysis of low-dose insulin signaling in murine muscle tissue, and report on the analytical and biological significance of our results.

The Spallation Neutron Source (SNS) was designed and constructed by a collaboration of six U.S. Department of Energy national laboratories. The SNS accelerator system consists of a 1 GeV linear accelerator and an accumulator ring providing 1.4 MW of proton beam power in microsecond-long beam pulses to a liquid mercury target for neutron production. The accelerator complex consists of a front-end negative hydrogen-ion injector system, an 87 MeV drift tube linear accelerator, a 186 MeV side-coupled linear accelerator, a 1 GeV superconducting linear accelerator, a 248-m circumference accumulator ring and associated beam transport lines. The accelerator complex is supported by ~100 high-power RF power systems, a 2 K cryogenic plant, ~400 DC and pulsed power supply systems, ~400 beam diagnostic devices and a distributed control system handling ~100,000 I/O signals. The beam dynamics design of the SNS accelerator is presented, as is the engineering design of the major accelerator subsystems.

The Solonker suture zone is one of the most important tectonic boundaries in the southeastern part of the Central Asian Orogenic Belt (CAOB). An ~ 630 km-long reflection seismic profile across this suture was recently completed by the Chinese SinoProbe Project. The processed seismic data show clear crustal structures and provide new constraints on the tectonic and crustal evolution models. The Moho is delineated as a relatively flat boundary between a strongly reflective lower crust and a transparent mantle at a depth of ~ 40–45 km (~ 14.5 s two-way travel time), which is in agreement with the refraction data recorded along the same profile. In a broad view, the profile images an orogen that appears bivergent with, and approximately centered on, the Solonker suture zone. The southern portion of this profile is dominated by a crustal-scale, cratonward propagating fold-and-thrust system that formed during the late Permian and Triassic through collision and subsequent convergence in a post-collisional stage. The major thrust faults are truncated by Mesozoic granitoid plutons in the upper crust and by the Moho at the base of the crust. This geometry suggests that the Moho was formed after the thrusting event. The northern portion of the profile, although partially obliterated by post-collisional magmatic bodies, shows major south-dipping folding and thrusting. Bands of layered reflectors immediately overlying the Moho are interpreted as basaltic sills derived from the mantle. Episodic mafic underplating may have occurred in this region, giving rise to post-collisional magmatic events and renewal of the Moho. A few mantle reflectors are also visible. The overall geometry of these mantle reflectors supports the tectonic models that the southern orogen (Manchurides) experienced south-directed subduction and the northern orogen (Altaids) underwent north-directed subduction prior to collision along the Solonker suture zone.

SUMMARY Targeted cancer therapeutics select for drug-resistant rescue subclones (RSCs), which typically carry rescue mutations that restore oncogenic signaling. Whereas mutations underlying antibiotic resistance frequently burden drug-naive microbes with a fitness cost, it remains unknown whether and how rescue mutations underlying cancer relapse encounter negative selection prior to targeted therapy. Here, using mouse models of reversible, Wnt-driven mam-mary cancer, we uncovered stringent counter-selection against Wnt signaling overdose during the clonal evolution of RSCs. Analyzing recurrent tumors emerging during simulated targeted therapy (Wnt withdrawal) by multi-region DNA sequencing revealed polyclonal relapses comprised of multiple RSCs, which bear distinct but functionally equivalent rescue mutations that converge on sub-maximal Wnt pathway activation. When superimposed on native (i.e., undrugged) signaling, these rescue mutations faced negative selection, indicating that they burden RSCs with a fitness cost before Wnt withdrawal unmasks their selective advantage. Exploiting collateral sensitivity to oncogene overdose may help eliminate RSCs and prevent cancer relapse., Graphical Abstract, In Brief Keller and Gunther show that Wnt-driven mammary cancers challenged with simulated targeted therapy (Wnt withdrawal) undergo clonal evolution, which stringently selects for mutations that restore a “just right” level of oncogenic signaling. Therefore, cancer relapses emerge from rare subclones that are encumbered by an untapped vulnerability to oncogene overdose.

The interaction between an energized size 14 American Wire Gauge (1.6 mm conductor diameter) nonmetallic-sheathed cable and a fire simulated using radiative heating was investigated. The time from the beginning of radiative exposure to an electrical arcing event was measured as a function of the heat flux and nominal alternating current voltage in air and nitrogen environments. The trends observed in these experiments were captured with simple mathematical expressions. Highly time-resolved voltage and current readings were collected around the time of the arcing events to better understand the dynamics of arc formation. These observations, together with cable insulation resistance measurements, were used to gain insight into the mechanism of heat flux induced cable failure. It was also demonstrated that a numerical pyrolysis model describing transient thermal degradation of cable insulation can be used to extrapolate the time of arc formation measurements conducted in this work to fire scenarios not realized in the cable testing experiments.

The current study examined the psychometric properties of the Brief Negative Symptom Scale (BNSS), a next-generation rating instrument developed in response to the NIMH sponsored consensus development conference on negative symptoms. Participants included 100 individuals with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who completed a clinical interview designed to assess negative, positive, disorganized, and general psychiatric symptoms, as well as functional outcome. A battery of anhedonia questionnaires and neuropsychological tests were also administered. Results indicated that the BNSS has excellent internal consistency and temporal stability, as well as good convergent and discriminant validity in its relationships with other symptom rating scales, functional outcome, self-reported anhedonia, and neuropsychological test scores. Given its brevity (13-items, 15-minute interview) and good psychometric characteristics, the BNSS can be considered a promising new instrument for use in clinical trials.

A series of 2-(1H-pyrazol-1-yl)pyridines are described as inhibitors of ALK5 (TGFβ receptor I kinase). Modeling compounds in the ALK5 kinase domain enabled some optimization of potency via substitutions on the pyrazole core. One of these compounds PF-03671148 gave a dose dependent reduction in TGFβ induced fibrotic gene expression in human fibroblasts. A similar reduction in fibrotic gene expression was observed when PF-03671148 was applied topically in a rat wound repair model. Thus these compounds have potential utility for the prevention of dermal scarring.

Electromigration (EM) of a dual damascene, test vehicle was measured using direct current (DC), alternating current (AC) followed by DC, and three rectangular-wave DC stressing conditions at 598K. In some of the experiments samples were allowed to cool to room temperature between the 598K stress cycles. We find that that only net DC time at test has a significant effect on time to fail. AC stressing for one week at 2.5MA/cm^2 prior to DC stressing to EM failure had no effect on the EM performance. A similar result is obtained with various DC and thermal cycling conditions. Thermal history of the EM test samples, and in particular cooling to room temperature, has no effect on EM lifetime. All tests, regardless of thermal history and current cycling conditions, resulted in statistically similar times to fail and distributions of those times. We conclude that the standard test methodologies, using accelerated DC stress conditions at elevated temperatures, are adequate. Since only the net DC stress time had any measurable effect on EM lifetime, the use of accelerated testing provides a good predictor for lifetime expectations under operating conditions. We also conclude that neither low current density AC stressing nor DC cycling, and associated changes to grain structure that may result, provide any measurable benefit to EM lifetime.

Objective To examine the structural integrity of the dorsolateral prefrontal-basal ganglia–thalamocortical circuit in people with the deficit form of schizophrenia. Method A three-dimensional structural MRI sequence was used to conduct morphometric assessments of cortical and subcortical regions in deficit and nondeficit outpatients with schizophrenia and healthy controls. Results The superior prefrontal and superior and middle temporal gyral gray matter volumes were significantly smaller in the deficit versus the nondeficit group and normal control groups. There were no significant group differences in examined subcortical structures. Conclusion People with deficit schizophrenia are characterized by selective reductions in the prefrontal and temporal cortex.

Pairs of rats foraged in trials either together or separately in an open field apparatus for pellets hidden in discreet locations in a 5 × 5 matrix. Trial duration was either 1 or 4 min. The tendency to choose locations that had earlier been visited by another rat was examined by comparing the choices made in the presence and absence of the other rat. Rats avoided visits to locations that had earlier been visited by the other rat, but only if they had also visited the same location earlier in a short duration trial. This pattern of results is consistent with earlier findings from experiments using the radial arm maze. Furthermore, when rats did visit locations that had earlier been visited by the other rat in a long duration trial, they tended to be locations that had been visited longer ago by the other rat than would be expected. This suggests a forgetting function for social memories. These data provide evidence that the social memory reported in earlier studies using the radial-arm maze can be found in other experimental paradigms and that at least some of its properties are common in the two paradigms.

Defining mechanisms that maintain tissue stem cells during homeostasis, stress, and aging is important for improving tissue regeneration and repair and enhancing cancer therapies. Here, we show that Id1 is induced in hematopoietic stem cells (HSCs) by cytokines that promote HSC proliferation and differentiation, suggesting that it functions in stress hematopoiesis. Genetic ablation of Id1 increases HSC self-renewal in serial bone marrow transplantation (BMT) assays, correlating with decreases in HSC proliferation, mitochondrial biogenesis, and reactive oxygen species (ROS) production. Id1-/- HSCs have a quiescent molecular signature and harbor less DNA damage than control HSCs. Cytokines produced in the hematopoietic microenvironment after γ-irradiation induce Id1 expression. Id1-/- HSCs display a blunted proliferative response to such cytokines and other inducers of chronic proliferation including genotoxic and inflammatory stress and aging, protecting them from chronic stress and exhaustion. Thus, targeting Id1 may be therapeutically useful for improving HSC survival and function during BMT, chronic stress, and aging.

A cantilever-based uncooled IR imager was developed utilizing a novel optical readout scheme based on inter-pixel interference. A series of small arrays (approximately 100 × 100 pixels) were fabricated using 8-in. silicon MEMS processes. The array design and process development will be discussed and initial uniformity and imaging results presented. Future challenges in developing a direct-view IR imager will be addressed.