While it no longer seems possible to speak of an invisible narrator of La princesse de Clèves, the 1678 historical novel by Madame de Lafayette, the notion of an invisible translator defines the work of late-twentieth-century English translations of the novel. According to this view, the translator should remain unseen by the reader and therefore “faithful” to the original text, so as not to upset the interpretive possibilities that Lafayette offers. In fact, however, the translator's infidelity is both necessary and vital to interpreting eros in La princesse de Clèves. The novel itself makes infidelity a form of insight, and Lafayette's vocabulary forces English translators into situations where any choice can be simultaneously unfaithful and correct. Like the character of the princess, translators have conflicting fidelities that should be made visible to fully reveal the richness of the novel.

OBJECTIVES/GOALS: To identify an electroencephalographic (EEG) signature of SOR in adults with TS METHODS/STUDY POPULATION: We will recruit 60 adults with CTD and 60 sex- and age-matched healthy controls to complete scales assessing severity of SOR (Sensory Gating Inventory, SGI), tics, and psychiatric symptoms. Subjects will then be monitored on dense-array scalp EEG during sequential auditory and tactile sensory gating paradigms, as such paradigms have been shown to correlate with self-report measures of SOR in other populations. Single-trial EEG data will be segmented into 100-ms epochs and spectrally deconvoluted into standard frequency bands (delta, theta, alpha, beta, gamma) for pre-defined regions of interest. We will conduct between-group contrasts (Wilcoxon rank-sum) of band-specific sensory gating indices and within-group correlations (Spearman rank correlations) between sensory gating indices and SGI scores. RESULTS/ANTICIPATED RESULTS: We hypothesize that, relative to controls, adults with CTD exhibit impaired sensory gating and that extent of impairment correlates with severity of SOR. 14 adults with CTD (9 men, 5 women) and 16 controls (10 men, 6 women) have completed the protocol to date. Within this sample, adults with CTD showed significantly reduced sensory gating compared to controls in frontal (CTD median 0.12 dB (interquartile range -0.15–0.70 dB); control -0.37 dB (-0.80–-0.13 dB); p = 0.01) and parietal (CTD 0.17 dB (-0.08–0.50 dB); control -0.20 dB (-0.43–0.10 dB); p = 0.01) gamma band during the 100-200 ms epoch in the tactile paradigm. No significant between-group differences were evident for the auditory paradigm. Among adults with CTD, multiple sensory gating indices significantly correlated with SGI scores. Enrollment continues. DISCUSSION/SIGNIFICANCE: Results aim to clarify the extent of sensory gating impairment in TS and identify a clinical correlate of neurophysiologic dysfunction in the disorder. Such knowledge has direct implications for identification of candidate neurophysiologic biomarkers, an express goal of the National Institutes of Health.

Understanding the distribution and geometry of faults and fractures is critical for predicting both subsurface permeability architecture and the integrity of geological fluid barriers, particularly in rocks with low primary porosity and permeability. While fracture patterns in relatively competent, weathering-resistant (therefore often well-exposed) rocks are generally well studied in outcrop, the role of mechanically weak layers in defining fracture patterns is frequently overlooked or under-represented. Here we show that rock composition, specifically clay and silicate minerals versus carbonate content, exerts a strong control on fault and fracture propagation and bed-containment within a mechanically layered, Cretaceous carbonate sequence at Canyon Lake Gorge, Texas. We find that relatively incompetent, clay-rich layers limit fault and fracture propagation, and cause bed-containment of fractures in more competent beds. In our results, no clear relationships exist between mechanical layer thickness and fracture abundance. These results are important for understanding the relative importance of composition versus bed thickness on fracture abundance in the subsurface, and for predicting fracture-controlled fluid flow pathways, seals and fracture connectivity across beds with variable compositions, thicknesses and competences.

Patients with liver cancer or space-occupying cysts suffer from malnutrition due to compression of gastric and digestive structures, liver and cancer-mediated dysmetabolism, and impaired nutrient absorption. As proportion of these patients requires removal of lesions through hepatic resection, it is important to evaluate the effects of malnutrition on post-hepatectomy outcomes. In our study approach, 2011–2017 National Inpatient Sample was used to isolate in-hospital hepatectomy cases, which were stratified using malnutrition (composite of malnutrition, sarcopenia and weight loss/cachexia). The malnutrition-absent controls were matched to cases using nearest neighbour propensity score matching method and compared with the following endpoints: mortality, length of stay, hospitalisation costs and postoperative complications. There were 2531 patients in total who underwent hepatectomy with matched number of controls from the database; following the match, malnutrition cohort (compared with controls) was more likely to experience in-hospital death (6·60 % v. 5·25 % P < 0·049, OR 1·27, 95 % CI 1·01, 1·61) and was more likely to have higher length of stay (18·10 d v. 9·32 d, P < 0·001) and hospitalisation costs ($278 780 v. $150 812, P < 0·001). In terms of postoperative complications, malnutrition cohort was more likely to experience bleeding (6·52 % v. 3·87 %, P < 0·001, OR 1·73, 95 % CI 1·34, 2·24), infection (6·64 % v. 2·49 %, P < 0·001, OR 2·79, 95 % CI 2·07, 3·74), wound complications (4·5 % v. 1·38 %, P < 0·001, OR 3·36, 95 % CI 2·29, 4·93) and respiratory failure (9·40 % v. 4·11 %, P < 0·001, OR 2·42, 95 % CI 1·91, 3·07). In multivariate analysis, malnutrition was associated with higher mortality (P < 0·028, adjusted OR 1·3, 95 % CI 1·03, 1·65). Thus, we conclude that malnutrition is a risk factor of postoperative mortality in patients undergoing hepatectomy.

ABSTRACT IMPACT: This work provides supporting evidence for the development of a novel immunosuppression therapy for transplant patients. OBJECTIVES/GOALS: Our laboratory reported that inhibition of the kinase DNA-PK(cs) in mice delays allogeneic graft rejection in part by mitigating the induction of certain cytokines. We hypothesized that this was due to an inhibition of intracellular signaling programs in T cells and designed studies to identify the mechanism(s) by which this occurs. METHODS/STUDY POPULATION: The immortalized Jurkat T cell line was used to evaluate the effect of the DNA-PK(cs) inhibitor NU7441 on T cell activation by PMA/Ionomycin or PMA/PHA. Mouse primary splenocytes also were used to demonstrate the universality and reproducibility of our observations. Initially, protein mass spectrometry of lysates from untreated and NU7441-treated Jurkat cells identified proteins of interest regulated by DNA-PK(cs) that play a role in T cell activation and cytokine production. CRISPR genome editing was used to validate a potential downstream target of DNA-PK(cs). Western blot, ELISA, and flow cytometry were used to document changes in protein levels with respect to treatments. RESULTS/ANTICIPATED RESULTS: We observed that expression of the transcription factor Egr1 was highly induced after activation but attenuated after treatment with NU7441 in both Jurkat T cells and mouse splenocytes. Phosphorylated serine 301 of Egr1 was identified by mass spectrometry in stimulated cells and fits the kinase consensus sequence for DNA-PK(cs). Both an endogenous CRISPR-generated serine 301 to alanine mutant and expression of a plasmid-based S301A mutant resulted in an unstable form of Egr1 that was barely detectable. In contrast, expression of either a S301 to D or E phospho-mimetic mutant resulted in a stable form of the protein detectable by Western blot. Further evaluation of these mutants and Egr1 phosphorylation is underway to determine the mechanism by which DNA-PK(cs) kinase regulates protein stability. DISCUSSION/SIGNIFICANCE OF FINDINGS: We previously reported a role for DNA-PK(cs) in immunomodulation. We now have evidence that this occurs in part through stabilization of Egr1. We believe this novel finding will lead to uncovering a broader role for DNA-PK(cs) as a mediator of protein stability in T cells and provide support for targeting DNA-PK(cs) in immunosuppression therapy.

Rough sleeping is a chronic experience faced by some of the most disadvantaged people in modern society. This paper describes work carried out in partnership with Homeless Link (HL), a UK-based charity, in developing a data-driven approach to better connect people sleeping rough on the streets with outreach service providers. HL's platform has grown exponentially in recent years, leading to thousands of alerts per day during extreme weather events; this overwhelms the volunteer-based system they currently rely upon for the processing of alerts. In order to solve this problem, we propose a human-centered machine learning system to augment the volunteers' efforts by prioritizing alerts based on the likelihood of making a successful connection with a rough sleeper. This addresses capacity and resource limitations whilst allowing HL to quickly, effectively, and equitably process all of the alerts that they receive. Initial evaluation using historical data shows that our approach increases the rate at which rough sleepers are found following a referral by at least 15% based on labeled data, implying a greater overall increase when the alerts with unknown outcomes are considered, and suggesting the benefit in a trial taking place over a longer period to assess the models in practice. The discussion and modeling process is done with careful considerations of ethics, transparency, and explainability due to the sensitive nature of the data involved and the vulnerability of the people that are affected.

Using an ensemble of close- and long-range remote sensing, lake bathymetry and regional meteorological data, we present a detailed assessment of the geometric changes of El Morado Glacier in the Central Andes of Chile and its adjacent proglacial lake between 1932 and 2019. Overall, the results revealed a period of marked glacier down wasting, with a mean geodetic glacier mass balance of −0.39 ± 0.15 m w.e.a−1 observed for the entire glacier between 1955 and 2015 with an area loss of 40% between 1955 and 2019. We estimate an ice elevation change of −1.00 ± 0.17 m a−1 for the glacier tongue between 1932 and 2019. The increase in the ice thinning rates and area loss during the last decade is coincident with the severe drought in this region (2010–present), which our minimal surface mass-balance model is able to reproduce. As a result of the glacier changes observed, the proglacial lake increased in area substantially between 1955 and 2019, with bathymetry data suggesting a water volume of 3.6 million m3 in 2017. This study highlights the need for further monitoring of glacierised areas in the Central Andes. Such efforts would facilitate a better understanding of the downstream impacts of glacier downwasting.

A field study was conducted in 2017 and 2018 to determine foliar efficacy of halauxifen-methyl, 2,4-D, or dicamba applied alone and in combination with glyphosate at preplant burndown timing. Experiments were conducted near Painter, VA; Rocky Mount, NC; Jackson, NC; and Gates, NC. Control of horseweed, henbit, purple deadnettle, cutleaf evening primrose, curly dock, purple cudweed, and common chickweed were evaluated. Halauxifen-methyl applied at 5 g ae ha−1 controlled small and large horseweed 89% and 79%, respectively, and was similar to control by dicamba applied at 280 g ae ha−1. Both rates of 2,4-D—533 g ae ha−1(low rate [LR]) or 1,066 g ae ha−1 (high rate [HR])—were less effective than halauxifen-methyl and dicamba for controlling horseweed. Halauxifen-methyl was the only auxin herbicide to control henbit (90%) and purple deadnettle (99%). Cutleaf evening primrose was controlled 74% to 85%, 51%, and 4% by 2,4-D, dicamba, and halauxifen-methyl, respectively. Dicamba and 2,4-D controlled curly dock 59% to 70% and were more effective than halauxifen-methyl (5%). Auxin herbicides applied alone controlled purple cudweed and common chickweed 21% or less. With the exception of cutleaf evening primrose (35%) and curly dock (37%), glyphosate alone provided 95% or greater control of all weeds evaluated. These experiments demonstrate halauxifen-methyl effectively (≥79%) controls horseweed, henbit, and purple deadnettle, whereas common chickweed, curly dock, cutleaf evening primrose, and purple cudweed control by the herbicide is inadequate (≤7%).

We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from $z = 0.35$ to 3; and a deep, high-redshift HI IM survey over 100 deg2 from $z = 3$ to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to $z \sim 3$ with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to $z = 6$ . These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.

Methionine, an essential sulphur-containing amino acid (SAA), plays an integral role in many metabolic processes. Evidence for the methionine requirements of adult dogs is limited, and we employed the indicator amino acid oxidation (IAAO) method to estimate dietary methionine requirements in Labrador retrievers (n 21). Using semi-purified diets, the mean requirement was 0·55 (95 % CI 0·41, 0·71) g/4184 kJ. In a subsequent parallel design study, three groups of adult Labrador retrievers (n 52) were fed semi-purified diets with 0·55 g/4184 kJ (test diet 1), 0·71 g/4184 kJ (test diet 2) or 1·37 g/4184 kJ (control diet) of methionine for 32 weeks to assess the long-term consequences of feeding. The total SAA content (2·68 g/4184 kJ) was maintained through dietary supplementation of cystine. Plasma methionine did not decrease in test group and increased significantly on test diet 1 in weeks 8 and 16 compared with control. Reducing dietary methionine did not have a significant effect on whole blood, plasma or urinary taurine or plasma N-terminal pro B-type natriuretic peptide. Significant effects in both test diets were observed for cholesterol, betaine and dimethylglycine. In conclusion, feeding methionine at the IAAO-estimated mean was sufficient to maintain plasma methionine over 32 weeks when total SAA was maintained. However, choline oxidation may have increased to support plasma methionine and have additional consequences for lipid metabolism. While the IAAO can be employed to assess essential amino acid requirements, such as methionine in the dog using semi-purified diets, further work is required to establish safe levels for commercial diet formats.

Active galactic nuclei (AGN) are believed to regulate star formation inside their host galaxies through “AGN feedback”. We summarise our on-going study of luminous AGN (z ∼ 0.2−3; LAGN,bol 1043 erg s−1), which is designed to search for observational signatures of feedback by combining observed star-formation rate (SFR) measurements from statistical samples with cosmological model predictions. Using the EAGLE hydrodynamical cosmological simulations, in combination with our Herschel + ALMA surveys, we show that – even in the presence of AGN feedback – we do not necessarily expect to see any relationships between average galaxy-wide SFRs and instantaneous AGN luminosities. We caution that the correlation with stellar mass for both SFR and AGN luminosity can contribute to apparent observed positive trends between these two quantities. On the other hand, the EAGLE simulations, which reproduce our observations, predict that a signature of AGN feedback can be seen in the wide specific SFR distributions of all massive galaxies (not just AGN hosts). Overall, whilst we can not rule out that AGN have an immediate small-scale impact on in-situ star-formation, all of our results are consistent with a feedback model where galaxy-wide in-situ star formation is not rapidly suppressed by AGN, but where the feedback likely acts over a longer timescale than a single AGN episode.

Rapeseed is a popular cover crop choice due to its deep-growing taproot, which creates soil macropores and increases water infiltration. Brassicaceae spp. that are mature or at later growth stages can be troublesome to control. Experiments were conducted in Delaware and Virginia to evaluate herbicides for terminating rapeseed cover crops. Two separate experiments, adjacent to each other, were established to evaluate rapeseed termination by 14 herbicide treatments at two timings. Termination timings included an early and late termination to simulate rapeseed termination prior to planting corn and soybean, respectively, for the region. At three locations where rapeseed height averaged 12 cm at early termination and 52 cm at late termination, glyphosate + 2,4-D was most effective, controlling rapeseed 96% 28 d after early termination (DAET). Paraquat + atrazine + mesotrione (92%), glyphosate + saflufenacil (91%), glyphosate + dicamba (91%), and glyphosate (86%) all provided at least 80% control 28 DAET. Rapeseed biomass followed a similar trend. Paraquat + 2,4-D (85%), glyphosate + 2,4-D (82%), and paraquat + atrazine + mesotrione (81%) were the only treatments that provided at least 80% control 28 d after late termination (DALT). Herbicide efficacy was less at Painter in 2017, where rapeseed height was 41 cm at early termination, and 107 cm at late termination. No herbicide treatments controlled rapeseed >80% 28 DAET or 28 DALT at this location. Herbicide termination of rapeseed is best when the plant is small; termination of large rapeseed plants may require mechanical of other methods beyond herbicides.

Residual herbicides are routinely applied to control troublesome weeds in pumpkin production. Fluridone and acetochlor, Groups 12 and 15 herbicides, respectively, provide broad-spectrum PRE weed control. Field research was conducted in Virginia and New Jersey to evaluate pumpkin tolerance and weed control to PRE herbicides. Treatments consisted of fomesafen at two rates, ethalfluralin, clomazone, halosulfuron, fluridone, S-metolachlor, acetochlor emulsifiable concentrate (EC), acetochlor microencapsulated (ME), and no herbicide. At one site, fluridone, acetochlor EC, acetochlor ME, and halosulfuron injured pumpkin 81%, 39%, 34%, and 35%, respectively, at 14 d after planting (DAP); crop injury at the second site was 40%, 8%, 19%, and 33%, respectively. Differences in injury between the two sites may have been due to the amount and timing of rainfall after herbicides were applied. Fluridone provided 91% control of ivyleaf morningglory and 100% control of common ragweed at 28 DAP. Acetochlor EC controlled redroot pigweed 100%. Pumpkin treated with S-metolachlor produced the most yield (10,764 fruits ha–1) despite broadcasting over the planted row; labeling requires a directed application to row-middles. A separate study specifically evaluated fluridone applied PRE at 42, 84, 126, 168, 252, 336, and 672 g ai ha–1. Fluridone resulted in pumpkin injury ≥95% when applied at rates of ≥168 g ai ha–1; significant yield loss was noted when the herbicide was applied at rates >42 g ai ha–1. We concluded that fluridone and acetochlor formulations are unacceptable candidates for pumpkin production.