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The EGS Collab project, supported by the US Department of Energy, is performing intensively monitored rock stimulation and flow tests at the 10-m scale in an underground research laboratory to address challenges in implementing enhanced geothermal systems (EGS). Data and observations from the field tests are compared to simulations to understand processes and build confidence in numerical modeling of the processes. We have completed Experiment 1 (of 3), which examined hydraulic fracturing in a well-characterized underground fractured phyllite test bed at a depth of approximately 1.5 km at the Sanford Underground Research Facility (SURF) in Lead, South Dakota. Testbed characterization included fracture mapping, borehole acoustic and optical televiewers, full waveform sonic, conductivity, resistivity, temperature, campaign p- and s-wave investigations and electrical resistance tomography. Borehole geophysical techniques including passive seismic, continuous active source seismic monitoring, electrical resistance tomography, fiber-based distributed strain, distributed temperature, and distributed acoustic monitoring, were used to carefully monitor stimulation events and flow tests. More than a dozen stimulations and nearly one year of flow tests were performed. Quality data and detailed observations were collected and analyzed during stimulation and water flow tests using ambient temperature and chilled water. We achieved adaptive control of the tests using real-time monitoring and rapid dissemination of data and near-real-time simulation. More detailed numerical simulation was performed to answer key experimental design questions, forecast fracture propagation trajectories and extents, and analyze and evaluate results. Data are freely available from the Geothermal Data Repository. Experiment 2 examines the potential for hydraulic shearing in amphibolite at a depth of about 1.25 km at SURF. This site has a different set of stress and fracture conditions than Experiment 1. The Experiment 2 testbed consists of nine subhorizontal boreholes configured in two fans of two boreholes which surround the testbed and contain grouted-in electrical resistance tomography, seismic sensors, active seismic sources and distributed fiber sensors. A “five-spot” set of test wells that extends from a custom mined alcove includes an injection well and four production/monitoring wells. The testbed was characterized geophysically and hydrologically, and three stimulations have been performed using the Step-Rate Injection Method for Fracture In-Situ Properties (SIMFIP) tool to measure strains, and a new strain quantifying tool (downhole robotic strain analysis tool -DORSA) was deployed in a monitoring hole during stimulation. Real-time data were broadcast during stimulations to allow real-time response to arising issues.

The EGS Collab project is performing well-monitored rock stimulation and flow tests at the 10-m scale in an underground research laboratory to inform challenges in implementing enhanced geothermal systems (EGS). This project, supported by the US Department of Energy, is gathering data and observations from the field tests and comparing these to simulation results to understand processes and to build confidence in numerical modeling of the processes. Experiment 1 (now complete) examined hydraulic fracturing in an underground test bed at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, at a depth of approximately 1.5 km in a well-characterized phyllite. Geophysical monitoring instrumentation in six of eight sub-horizontal boreholes monitored stimulation events and flow tests. The other two boreholes were used to perform and carefully measure water injection and production. More than a dozen stimulations and nearly one year of flow tests in the testbed were performed. Detailed observations of processes occurring during stimulation and dynamic flow tests were collected and analyzed. Flow tests using ambient-temperature and chilled water were performed with intermittent tracer tests to examine system behavior. We achieved adaptive control of the tests using close monitoring of rapidly disseminated data and near-real-time simulation. Numerical simulation was critical in answering key experimental design questions, forecasting fracture behavior, and analyzing results. We were successful in performing many simulations in near-real-time in conjunction with the field experiments, with more detailed simulations performed later. The primary objective of Experiment 2 is to examine hydraulic shearing of natural fractures at a depth of 1.25 km in amphibolite at SURF. The stresses, rock type, and fracture conditions are different than in Experiment 1. The testbed consists of 9 boreholes, in addition to two earlier-drilled characterization boreholes. One borehole is used for injection, two fans of 2 monitoring wells have several geophysical measurement tools grouted in, and four open boreholes surrounding the injection hole are adaptively used for production and monitoring. We have encountered approximately five fracture set orientations in the testbed, and designed our testbed accordingly to maximize the potential for shear stimulation. Three stimulations have been performed to date from the injection borehole, each intersecting at least one production borehole. Different methods have been used for each stimulation, including a ramped flow, a high flow rate, and oscillating pressure.

To pinpoint difficulties in the second language (L2) processing of temporarily ambiguous sentences, this study investigates first language (L1) effects and effects of verb bias, i.e. frequency information about preferential verb complements, on semantic persistence effects in L2 sentence comprehension. We tested 32 L1 German and 32 L1 Turkish intermediate-to-advanced learners of L2 English as well as 17 English natives in eye-tracking during reading and off-line comprehension. In off-line comprehension, neither natives nor L2 learners show verb bias effects, suggesting that semantic persistence of initial misinterpretations arises independently of lexical preferences. In contrast, reading times show that all groups are immediately sensitive to verb bias on-line, with L1 differences in how strongly verb bias affects garden-pathing. Unlike natives, however, L2 learners do not use verb bias to overcome semantic persistence to complete reanalysis in later segments of the sentence. We argue that, in spite of their initial sensitivity to verb bias in modulating garden paths, L2 readers suffer from processing limitations that constrain their ability to retrieve and integrate multiple sources of information for reanalysis. Our study confirms that reanalysis constitutes a key area of native versus non-native differences in L2 sentence processing.

The Hobby-Eberly Telescope (HET) Dark Energy Experiment (HETDEX) is undertaking a blind wide-field low-resolution spectroscopic survey of 540 deg2 of sky to identify and derive redshifts for a million Lyα-emitting galaxies in the redshift range 1.9 < z < 3.5. The ultimate goal is to measure the expansion rate of the universe at this epoch, to sharply constrain cosmological parameters and thus the nature of dark energy. A major multiyear Wide-Field Upgrade (WFU) of the HET was completed in 2016 that substantially increased the field of view to 22′ diameter and the pupil to 10 m, by replacing the optical corrector, tracker, and Prime Focus Instrument Package and by developing a new telescope control system. The new, wide-field HET now feeds the Visible Integral-field Replicable Unit Spectrograph (VIRUS), a new low-resolution integral-field spectrograph (LRS2), and the Habitable Zone Planet Finder, a precision near-infrared radial velocity spectrograph. VIRUS consists of 156 identical spectrographs fed by almost 35,000 fibers in 78 integral-field units arrayed at the focus of the upgraded HET. VIRUS operates in a bandpass of 3500-5500 Å with resolving power R ≃ 800. VIRUS is the first example of large-scale replication applied to instrumentation in optical astronomy to achieve spectroscopic surveys of very large areas of sky. This paper presents technical details of the HET WFU and VIRUS, as flowed down from the HETDEX science requirements, along with experience from commissioning this major telescope upgrade and the innovative instrumentation suite for HETDEX.

We describe the survey design, calibration, commissioning, and emission-line detection algorithms for the Hobby–Eberly Telescope Dark Energy Experiment (HETDEX). The goal of HETDEX is to measure the redshifts of over a million Lyα emitting galaxies between 1.88 < z < 3.52, in a 540 deg2 area encompassing a comoving volume of 10.9 Gpc3. No preselection of targets is involved; instead the HETDEX measurements are accomplished via a spectroscopic survey using a suite of wide-field integral field units distributed over the focal plane of the telescope. This survey measures the Hubble expansion parameter and angular diameter distance, with a final expected accuracy of better than 1%. We detail the project’s observational strategy, reduction pipeline, source detection, and catalog generation, and present initial results for science verification in the Cosmological Evolution Survey, Extended Groth Strip, and Great Observatories Origins Deep Survey North fields. We demonstrate that our data reach the required specifications in throughput, astrometric accuracy, flux limit, and object detection, with the end products being a catalog of emission-line sources, their object classifications, and flux-calibrated spectra.

Studies show teaching assistants (TAs) can positively influence the learning environment by increasing student comprehension and retention and impacting students' choices of academic and career paths. However, use of TAs in higher education is not universal. Following a fruitful panel discussion at the 2017 HAPS Conference, we conducted a survey to assess the prevalence of undergraduate and graduate TAs in human anatomy and physiology courses across a range of institutions and to evaluate how TAs are recruited, trained and compensated. Data from 329 respondents who used TAs, indicate most institutions use a formal application process, training procedures vary, and most TAs are compensated financially through hourly wages, stipends, or tuition credit. However, some TAs are unpaid but receive course credit as compensation. We highlight one of the more successful recruiting and training programs, where paid master TAs mentor unpaid apprentice TAs. This tiered training program excites and motivates student leadership, maintains high academic standards, and alleviates the lead instructor from continually training novice TAs.

Abstract Dysregulation of pathogen-recognition pathways of the innate immune system is associated with multiple autoimmune disorders. Due to the intricacies of the molecular network involved, the identification of pathway- and disease-specific therapeutics has been challenging. Using a phenotypic assay monitoring the degradation of the immune adapter TASL, we identify feeblin, a chemical entity which inhibits the nucleic acid-sensing TLR7/8 pathway activating IRF5 by disrupting the SLC15A4-TASL adapter module. A high-resolution cryo-EM structure of feeblin with SLC15A4 reveals that the inhibitor binds a lysosomal outward-open conformation incompatible with TASL binding on the cytoplasmic side, leading to degradation of TASL. This mechanism of action exploits a conformational switch and converts a target-binding event into proteostatic regulation of the effector protein TASL, interrupting the TLR7/8-IRF5 signaling pathway and preventing downstream proinflammatory responses. Considering that all components involved have been genetically associated with systemic lupus erythematosus and that feeblin blocks responses in disease-relevant human immune cells from patients, the study represents a proof-of-concept for the development of therapeutics against this disease.

O objetivo do estudo foi descrever e discutir o desenvolvimento de uma tecnologia social para educação em saúde por meio da técnica de gamificação. A pesquisa descritiva relatou a utilização do Design Thinking para gamificação de conhecimentos sobre saúde, a partir da produção de um jogo de tabuleiro, visando a educação em saúde com base nos princípios da tecnologia social. A construção do “Caminhos do SUS” foi consequência de um método participativo e colaborativo, que partiu de demandas reais da comunidade escolar, identificadas em um diálogo horizontal com os diferentes atores sociais. No jogo de tabuleiro, o jogador percorre diversos dispositivos de saúde e cuidado, cuja missão é resolver problemáticas da vida diária. A ação teve como público-alvo escolares maiores de 12 anos, que deveriam descobrir os locais e os serviços da cidade, seguindo o fluxo de encaminhamentos e relacionando as informações técnicas apresentadas nas cartas aos seus saberes e aos de seus colegas. Assim, esse processo configurou-se como uma ação de educação em saúde para a multiplicação de conhecimentos sobre o SUS. Concluiu-se que o “Caminhos do SUS” é uma potente ferramenta, capaz de gerar transformação social a partir da produção de autonomia e senso de comunidade, sendo possível sua utilização como uma tecnologia social inovadora para educação em saúde.

This paper investigates the interplay between open innovation activities and entrepreneurial intentions in the commercialization process of research results originating from academia. Through qualitative case study research, we identify theoretical mechanisms through the qualitative analysis of five case studies. Our results show that inbound and coupled open innovation activities compensate for lower entrepreneurial intentions among academically oriented scientists. However, establishing partnerships remains challenging, particularly in pre-prototyping phases. Nevertheless, our findings point towards social entrepreneurial intentions as fruitful avenues for stimulating entrepreneurial behaviour in academic scientists

A wide variety of control and surveillance programmes that are designed and implemented based on country-specific conditions exists for infectious cattle diseases that are not regulated. This heterogeneity renders difficult the comparison of probabilities of freedom from infection estimated from collected surveillance data. The objectives of this review were to outline the methodological and epidemiological considerations for the estimation of probabilities of freedom from infection from surveillance information and review state-of-the-art methods estimating the probabilities of freedom from infection from heterogeneous surveillance data. Substantiating freedom from infection consists in quantifying the evidence of absence from the absence of evidence. The quantification usually consists in estimating the probability of observing no positive test result, in a given sample, assuming that the infection is present at a chosen (low) prevalence, called the design prevalence. The usual surveillance outputs are the sensitivity of surveillance and the probability of freedom from infection. A variety of factors influencing the choice of a method are presented; disease prevalence context, performance of the tests used, risk factors of infection, structure of the surveillance programme and frequency of testing. The existing methods for estimating the probability of freedom from infection are scenario trees, Bayesian belief networks, simulation methods, Bayesian prevalence estimation methods and the STOC free model. Scenario trees analysis is the current reference method for proving freedom from infection and is widely used in countries that claim freedom. Bayesian belief networks and simulation methods are considered extensions of scenario trees. They can be applied to more complex surveillance schemes and represent complex infection dynamics. Bayesian prevalence estimation methods and the STOC free model allow freedom from infection estimation at the herd-level from longitudinal surveillance data, considering risk factor information and the structure of the population. Comparison of surveillance outputs from heterogeneous surveillance programmes for estimating the probability of freedom from infection is a difficult task. This paper is a ‘guide towards substantiating freedom from infection’ that describes both all assumptions-limitations and available methods that can be applied in different settings.

Eucalyptus dunnii is one of the most important Eucalyptus species for short-fiber pulp production in regions where other species of the genus are affected by poor soil and climatic conditions. In this context, E. dunnii holds promise as a resource to address and adapt to the challenges of climate change. Despite its rapid growth and favorable wood properties for solid wood products, the advancement of its improvement remains in its early stages. In this work, we evaluated the performance of two single nucleotide polymorphism, (SNP), genotyping methods for population genetics analysis and Genomic Selection in E. dunnii. Double digest restriction-site associated DNA sequencing (ddRADseq) was compared with the EUChip60K array in 308 individuals from a provenance-progeny trial. The compared SNP set included 8,011 and 19,008 informative SNPs distributed along the 11 chromosomes, respectively. Although the two datasets differed in the percentage of missing data, genome coverage, minor allele frequency and estimated genetic diversity parameters, they revealed a similar genetic structure, showing two subpopulations with little differentiation between them, and low linkage disequilibrium. GS analyses were performed for eleven traits using Genomic Best Linear Unbiased Prediction (GBLUP) and a conventional pedigree-based model (ABLUP). Regardless of the SNP dataset, the predictive ability (PA) of GBLUP was better than that of ABLUP for six traits (Cellulose content, Total and Ethanolic extractives, Total and Klason lignin content and Syringyl and Guaiacyl lignin monomer ratio). When contrasting the SNP datasets used to estimate PAs, the GBLUP-EUChip60K model gave higher and significant PA values for six traits, meanwhile, the values estimated using ddRADseq gave higher values for three other traits. The PAs correlated positively with narrow sense heritabilities, with the highest correlations shown by the ABLUP and GBLUP-EUChip60K. The two genotyping methods, ddRADseq and EUChip60K, are generally comparable for population genetics and genomic prediction, demonstrating the utility of the former when subjected to rigorous SNP filtering. The results of this study provide a basis for future whole-genome studies using ddRADseq in non-model forest species for which SNP arrays have not yet been developed.

This article explores how multiple linguistic cues interact in predictive processing among second language (L2) learners. In a visual-world eye-tracking experiment, we investigated whether learners of German use case and prosody cues together to assign thematic roles and predict post-verbal arguments. During the experiment, participants listened to subject-first and object-first sentences that contained (1) case cues only, or (2) both case and prosody. The results showed that the learners successfully predicted post-verbal arguments on the basis of lexical-semantic information but were less successful in using case cues. However, prediction success increased when both case and prosody were present, suggesting that predictive processing is supported by prosodic cues. Additionally, results show that higher proficiency was associated with faster processing and a greater ability to generate predictions. We conclude that the presence of cue coalitions allows L2 learners to process information more efficiently, and that the L2 processor can exploit the additive use of cues for prediction.

ObjectiveIncompletely resected epithelial ovarian cancer represents a poor prognostic subset of patients. Novel treatment strategies are needed to improve outcomes for this population. We evaluated a treatment strategy combining platinum-based chemotherapy with pembrolizumab followed by pembrolizumab maintenance therapy in the first-line treatment after incomplete resection of epithelial ovarian cancer patients.MethodsThis was a single-arm, non-randomized pilot study of carboplatin, taxane, and immune checkpoint inhibitor, pembrolizumab, followed by 12 months of maintenance pembrolizumab in patients with incompletely resected epithelial ovarian cancer (EOC).ResultsA total of 29 patients were enrolled and evaluated for efficacy and safety. The best response to therapy was complete response in 16 (55%) patients, partial response in 9 (31%) patients, and 3 (10%) patients with progression of disease. The median progression-free survival (PFS) was 13.2 months. Grade 3 and 4 toxicities occurred in 20% of patients. In all, 7 patients discontinued therapy due to adverse events. Quality-of-life scores remained high during therapy. Response to therapy did not correlate with PD-L1 tumor expression.ConclusionsCombination platinum–taxane therapy with pembrolizumab did not increase median progression-free survival in this cohort of patients.Key messageEOC is an immunogenic disease, but immune checkpoint inhibitor therapy has yet to impact outcomes. The current study utilized pembrolizumab in combination with standard chemotherapy followed by a maintenance treatment strategy in incompletely resected EOC. Progression-free survival was not extended in this poor prognostic group with combined chemotherapy and immunotherapy.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT 027766582.

Moral judgments are shaped by socialization and cultural heritage. Understanding how moral considerations vary across the globe requires the systematic development of moral stimuli for use in different cultures and languages. Focusing on Dutch populations, we adapted and validated two recent instruments for examining moral judgments: (1) the Moral Foundations Vignettes (MFVs) and (2) the Socio-Moral Image Database (SMID). We translated all 120 MFVs from English into Dutch and selected 120 images from SMID that primarily display moral, immoral, or neutral content. A total of 586 crowd-workers from the Netherlands provided over 38,460 individual judgments for both stimuli sets on moral and affective dimensions. For both instruments, we find that moral judgments and relationships between the moral foundations and political orientation are similar to those reported in the US, Australia, and Brazil. We provide the validated MFV and SMID images, along with associated rating data, to enable a broader study of morality.