Herbaceous perennials must annually rebuild the aboveground photosynthetic architecture from carbohydrates stored in crowns, rhizomes, and roots. Knowledge of carbohydrate utilization and storage can inform management decisions and improve control outcomes for invasive perennials. We monitored the nonstructural carbohydrates in a population of the hybrid Bohemian knotweed [Polygonum ×bohemicum (J. Chrtek & Chrtková) Zika & Jacobson [cuspidatum × sachalinense]; syn.: Fallopia ×bohemica (Chrtek and Chrtková) J.P. Bailey] and in Japanese knotweed [Polygonum cuspidatum Siebold & Zucc.; syn.: Fallopia japonica (Houtt.) Ronse Decr.]. Carbohydrate storage in crowns followed seasonal patterns typical of perennial herbaceous dicots corresponding to key phenological events. Starch was consistently the highest nonstructural carbohydrate present. Sucrose levels did not show a consistent inverse relationship with starch levels. Lateral distribution of starch in rhizomes and, more broadly, total nonstructural carbohydrates sampled before dormancy break showed higher levels in rhizomes compared with crowns. Total nonstructural carbohydrate levels in crowns reached seasonal lows at an estimated 22.6% of crown dry weight after accumulating 1,453.8 growing degree days (GDD) by the end of June, mainly due to depleted levels of stored starch, with the estimated minimum of 12.3% reached by 1,220.3 GDD accumulated by mid-June. Depletion corresponded to rapid development of vegetative canopy before entering the reproductive phase in August. Maximum starch accumulation in crowns followed complete senescence of aboveground tissues by mid- to late October. Removal of aboveground shoot biomass in late June to early July with removal of vegetation regrowth in early September before senescence would optimize the use of time and labor to deplete carbohydrate reserves. Additionally, foliar-applied systemic herbicide translocation to belowground tissue should be maximized with applications in late August through early fall to optimize downward translocation with assimilate movement to rebuild underground storage reserves. Fall applications should be made before loss of healthy leaf tissue, with the window for control typically ending by late September in Minnesota.

Area-based conservation is a widely used approach for maintaining biodiversity, and there are ongoing discussions over what is an appropriate global conservation area coverage target. To inform such debates, it is necessary to know the extent and ecological representativeness of the current conservation area network, but this is hampered by gaps in existing global datasets. In particular, although data on privately and community-governed protected areas and other effective area-based conservation measures are often available at the national level, it can take many years to incorporate these into official datasets. This suggests a complementary approach is needed based on selecting a sample of countries and using their national-scale datasets to produce more accurate metrics. However, every country added to the sample increases the costs of data collection, collation and analysis. To address this, here we present a data collection framework underpinned by a spatial prioritization algorithm, which identifies a minimum set of countries that are also representative of 10 factors that influence conservation area establishment and biodiversity patterns. We then illustrate this approach by identifying a representative set of sampling units that cover 10% of the terrestrial realm, which included areas in only 25 countries. In contrast, selecting 10% of the terrestrial realm at random included areas across a mean of 162 countries. These sampling units could be the focus of future data collation on different types of conservation area. Analysing these data could produce more rapid and accurate estimates of global conservation area coverage and ecological representativeness, complementing existing international reporting systems.

Until recently, the influence of basal liquid water on the evolution of buried glaciers in Mars' mid latitudes was assumed to be negligible because the latter stages of Mars' Amazonian period (3 Ga to present) have long been thought to have been similarly cold and dry to today. Recent identifications of several landforms interpreted as eskers associated with these young (100s Ma) glaciers calls this assumption into doubt. They indicate basal melting (at least locally and transiently) of their parent glaciers. Although rare, they demonstrate a more complex mid-to-late Amazonian environment than was previously understood. Here, we discuss several open questions posed by the existence of glacier-linked eskers on Mars, including on their global-scale abundance and distribution, the drivers and dynamics of melting and drainage, and the fate of meltwater upon reaching the ice margin. Such questions provide rich opportunities for collaboration between the Mars and Earth cryosphere research communities.

When participants in psychophysical experiments are asked to estimate or identify stimuli which differ on a single physical dimension, their judgments are influenced by the local experimental context — the item presented and judgment made on the previous trial. It has been suggested that similar sequential effects occur in more naturalistic, real-world judgments. In three experiments we asked participants to judge the prices of a sequence of items. In Experiment 1, judgments were biased towards the previous response (assimilation) but away from the true value of the previous item (contrast), a pattern which matches that found in psychophysical research. In Experiments 2A and 2B, we manipulated the provision of feedback and the expertise of the participants, and found that feedback reduced the effect of the previous judgment and shifted the effect of the previous item's true price from contrast to assimilation. Finally, in all three experiments we found that judgments were biased towards the centre of the range, a phenomenon known as the “regression effect” in psychophysics. These results suggest that the most recently-presented item is a point of reference for the current judgment. The findings inform our understanding of the judgment process, constrain the explanations for local context effects put forward by psychophysicists, and carry practical importance for real-world situations in which contextual bias may degrade the accuracy of judgments.

We examine temporal and spatial variation in morphology of the ammonoid cephalopod Discoscaphites iris using a large dataset from multiple localities in the Late Cretaceous (Maastrichtian) of the U.S. Gulf and Atlantic Coastal Plains, spanning a distance of 2000 km along the paleoshoreline. Our results suggest that the fossil record of D. iris is consistent with no within-species net accumulation of phyletic evolutionary change across morphological traits or the lifetime of this species. Correlations between some traits and paleoenvironmental conditions as well as changes in the coefficient of variation may support limited population-scale ecophenotypic plasticity; however, where stratigraphic data are available, no directional changes in morphology occur before the Cretaceous/Paleogene (K/Pg) boundary. This is consistent with models of “dynamic” evolutionary stasis. Combined with knowledge of life-history traits and paleoecology of scaphitid ammonoids, specifically a short planktonic phase after hatching followed by transition to a nektobenthic adult stage, these data suggest that scaphitids had significant potential for rapid morphological change in conjunction with limited dispersal capacity. It is therefore likely that evolutionary mode in the Scaphitidae (and potentially across the broader ammonoid clade) follows a model of cladogenesis wherein a dynamic morphological stasis is periodically interrupted by more substantial evolutionary change at speciation events. Finally, the lack of temporal changes in our data suggest that global environmental changes had a limited effect on the morphology of ammonoid faunas during the latest Cretaceous.

Knotweed (Fallopia spp.) is an herbaceous perennial from East Asia that was brought to Europe and North America and, despite control efforts, subsequently spread aggressively on both continents. Data are available on knotweed’s modes of sexual and asexual spread, historical spread, preferred habitat, and ploidy levels. Incomplete information is available on knotweed’s current global geographic distribution and genetic diversity. The chemical composition of knotweed leaves and rhizomes has been partially discovered as related to its ability to inhibit growth and germination of neighboring plant communities via phytochemicals. There is still critical information missing. There are currently no studies detailing knotweed male and female fertility. Specifically, information on pollen viability would be important for further understanding sexual reproduction as a vector of spread in knotweed. This information would help managers determine the potential magnitude of knotweed sexual reproduction and the continued spread of diverse hybrid swarms. The potential range of knotweed and its ability to spread into diverse habitats makes studies on knotweed seed and rhizome cold tolerance of utmost importance, yet to date no such studies have been conducted. There is also a lack of genetic information available on knotweed in the upper Midwest. Detailed genetic information, such as ploidy levels and levels of genetic diversity, would answer many questions about knotweed in Minnesota, including understanding its means of spread, what species are present in what densities, and current levels of hybridization. This literature review summarizes current literature on knotweed to better understand its invasiveness and to highlight necessary future research that would benefit and inform knotweed management in the upper Midwest.

In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a “wet” person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.

This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.

This article argues that post-conflict consociational arrangements in ethnically divided societies incentivize moderation by political parties, but not policy differentiation outside the main conflict. This results in little policy-driven voting. Analysing party manifestos and voter survey data, we examine the evolution of party policy and cleavage voting under power-sharing in Northern Ireland 1998–2016. We find a reduction in ethno-national policy differences between parties and that ethno-nationalism has become less important in predicting vote choice for Protestants, but not Catholics. We also find little party differentiation in other policy areas and show that vote choices are largely independent of people's policy stances on economic or social issues. Our findings are thus largely consistent with a ‘top-down’ interpretation of political dynamics.

OBJECTIVES/SPECIFIC AIMS: Objective: apply checkpoint inhibitors that are specific to the exhaustive markers expressed on tumor CD8+ T-cells ex vivo in order to improve cytokine release and cytotoxic function in comparison to two control groups: (1.) T-cells that receive no antibodies; (2.) T-cells that receive standard inhibition with PD-1 and CTLA-4 antibodies only. Long-term objective: provide personalized medicine in the treatment of HCC by using checkpoint inhibitors that are specific to the receptors expressed by an individual tumor. METHODS/STUDY POPULATION: The study population includes patients undergoing liver transplantation or surgical resection for HCC. Two grams of tumor, two grams of healthy liver tissue at least one centimeter from the tumor margin, and 50 milliliters of blood will be obtained. Solid tissue will be mechanically and enzymatically disrupted and CD8+ T-cells will be isolated from all sites. Using flow cytometry, the expression of surface receptors PD-1, CTLA-4, LAG-3, TIM-3, BTLA, CD244, and CD160 will be categorized in each tissue to identify which receptors are upregulated in the tumor microenvironment. Up to three antibodies specific to the upregulated receptor(s) on the tumor T-cells will be applied per specimen. The experimental arm will receive these antibodies and co-stimulation with CD3/CD28 and will be compared to two controls. One control will receive only CD3/CD28, and the other will receive CD3/CD28 in addition to the standard combination of PD-1 and CTLA-4 inhibitors. From each condition, flow cytometry will be used to assess the mean production of interleukin-2, tumor necrosis factor-α, interferon-γ, granzyme B, and perforin expression as an assessment of T-cell function. RESULTS/ANTICIPATED RESULTS: Preliminary data from the peripheral blood of healthy controls confirms that the developed flow cytometry panels effectively identify the surface receptors and cytokine production of CD8+ T-cells. Two patients have successfully been enrolled in this study. It is predicted that T-cells extracted from the tumor will express more inhibitory receptors than normal liver or peripheral blood and will have increased function after they are targeted with checkpoint inhibitors that are specific to the inhibitory surface receptors they express. DISCUSSION/SIGNIFICANCE OF IMPACT: HCC is the second leading cause of cancer-related death worldwide and therapeutic options are limited for patients who are not surgical candidates. T-cells are a critical component of the anti-tumor response to HCC. However, T-cells can develop an exhausted phenotype characterized by up-regulated inhibitory receptors (PD-1, CTLA-4, LAG-3, TIM-3, CD-244, CD-160, BTLA) and decreased function, allowing for immune escape. Clinical trials using combined checkpoint inhibition with PD-L1 and CTLA-4 antibodies have been considered a breakthrough for patients with advanced HCC, as up to 25% show an objective tumor response. The explanation for the varied susceptibility to checkpoint inhibition remains unknown and is hypothesized to be secondary to inconsistencies in the expression of surface inhibitory receptors. Although inhibitory receptor expression has been shown to be upregulated under conditions of hepatitis and/or HCC, there has been no single study to effectively investigate the expression of all known inhibitors in order to better explore the interplay between them. It will be of great academic interest and clinical purpose to evaluate individual receptor expression and engage the correlating antibodies given the possibility of synergism between receptors and the need for a more profound anti-tumor T-cell response in HCC.

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.

We carry out a numerical study of the quantum walk search algorithm of Shenvi, Kempe and Whaley Shenvi et al. (2003) and the factors that affect its efficiency in finding an individual state from an unsorted set. Previous work has focused purely on the effects of the dimensionality of the dataset to be searched. In the current paper we consider the effects of interpolating between dimensions, the connectivity of the dataset and the possibility of disorder in the underlying substrate: all these factors affect the efficiency of the search algorithm. We show that in addition to the strong dependence on the spatial dimension of the structure to be searched, there are also secondary dependencies on the connectivity and symmetry of the lattice, with greater connectivity providing a more efficient algorithm. We also show that the algorithm can tolerate a non-trivial level of disorder in the underlying substrate.