263 research outputs found

    The anticipatory and task-driven nature of visual perception

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    Modular Synthesis of Sketches Using Models

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    One problem with the constraint-based approaches to synthesis that have become popular over the last few years is that they only scale to relatively small routines, on the order of a few dozen lines of code. This paper presents a mechanism for modular reasoning that allows us to break larger synthesis problems into small manageable pieces. The approach builds on previous work in the verification community of using high-level specifications and partially interpreted functions (we call them models) in place of more complex pieces of code in order to make the analysis modular. The main contribution of this paper is to show how to combine these techniques with the counterexample guided synthesis approaches used to efficiently solve synthesis problems. Specifically, we show two new algorithms; one to efficiently synthesize functions that use models, and another one to synthesize functions while ensuring that the behavior of the resulting function will be in the set of behaviors allowed by the model. We have implemented our approach on top of the open-source Sketch synthesis system, and we demonstrate its effectiveness on several Sketch benchmark problems.National Science Foundation (U.S.) (Grant NSF-1116362)National Science Foundation (U.S.) (Grant NSF-1139056)United States. Dept. of Energy (Grant DE-SC0005372

    Tibiofemoral Contact Forces in the Anterior Cruciate Ligament-Reconstructed Knee.

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    PURPOSE: To investigate differences in ACL reconstructed (ACLR) and healthy individuals in terms of the magnitude of the tibiofemoral contact forces, as well as the relative muscle and external load contributions to those contact forces, during walking, running and sidestepping gait tasks. METHODS: A computational electromyography-driven neuromusculoskeletal model was used to estimate the muscle and tibiofemoral contact forces in those with combined semitendinosus and gracilis tendon autograft ACLR (n=104, 29.7±6.5 years, 78.1±14.4 kg) and healthy controls (n=60, 27.5±5.4 years, 67.8±14.0 kg) during walking (1.4±0.2 ms), running (4.5±0.5 ms) and sidestepping (3.7±0.6 ms). Within the computational model, the semitendinosus of ACLR participants was adjusted to account for literature reported strength deficits and morphological changes subsequent to autograft harvesting. RESULTS: ACLRs had smaller maximum total and medial tibiofemoral contact forces (~80% of control values, scaled to bodyweight) during the different gait tasks. Compared to controls, ACLRs were found to have a smaller maximum knee flexion moment, which explained the smaller tibiofemoral contact forces. Similarly, compared to controls, ACLRs had both a smaller maximum knee flexion angle and knee flexion excursion during running and sidestepping, which may have concentrated the articular contact forces to smaller areas within the tibiofemoral joint. Mean relative muscle and external load contributions to the tibiofemoral contact forces were not significantly different between ACLRs and controls. CONCLUSION: ACLRs had lower bodyweight-scaled tibiofemoral contact forces during walking, running and sidestepping, likely due to lower knee flexion moments and straighter knee during the different gait tasks. The relative contributions of muscles and external loads to the contact forces were equivalent between groups

    Partial model checking with ROBDDs

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    Mesoscopic scattering in the half-plane: squeezing conductance through a small hole

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    We model the 2-probe conductance of a quantum point contact (QPC), in linear response. If the QPC is highly non-adiabatic or near to scatterers in the open reservoir regions, then the usual distinction between leads and reservoirs breaks down and a technique based on scattering theory in the full two-dimensional half-plane is more appropriate. Therefore we relate conductance to the transmission cross section for incident plane waves. This is equivalent to the usual Landauer formula using a radial partial-wave basis. We derive the result that an arbitrarily small (tunneling) QPC can reach a p-wave channel conductance of 2e^2/h when coupled to a suitable reflector. If two or more resonances coincide the total conductance can even exceed this. This relates to recent mesoscopic experiments in open geometries. We also discuss reciprocity of conductance, and the possibility of its breakdown in a proposed QPC for atom waves.Comment: 8 pages, 3 figures, REVTeX. Revised version (shortened), accepted for publication in PR

    A 100-Year Review: A century of change in temperate grazing dairy systems

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    peer-reviewedFrom 1917 to 2017, dairy grazing systems have evolved from uncontrolled grazing of unimproved pastures by dual-purpose dairy-beef breeds to an intensive system with a high output per unit of land from a fit-for-purpose cow. The end of World War I signaled significant government investments in agricultural research institutes around the world, which coincided with technological breakthroughs in milk harvesting and a recognition that important traits in both plants and animals could be improved upon relatively rapidly through genetic selection. Uptake of milk recording and herd testing increased rapidly through the 1920s, as did the recognition that pastures that were rested in between grazing events yielded more in a year than those continuously grazed. This, and the invention and refinement of the electric fence, led to the development of “controlled” rotational grazing. This, in itself, facilitated greater stocking rates and a 5 to 10% increase in milk output per hectare but, perhaps more importantly, it allowed a more efficient use of nitrogen fertilizer, further increasing milk output/land area by 20%. Farmer inventions led to the development of the herringbone and rotary milking parlors, which, along with the “unshortable” electric fence and technological breakthroughs in sperm dilution rates, allowed further dairy farm expansion. Simple but effective technological breakthroughs in reproduction ensured that cows were identified in estrus early (a key factor in maintaining the seasonality of milk production) and enabled researchers to quantify the anestrus problem in grazing herds. Genetic improvement of pasture species has lagged its bovine counterpart, but recent developments in multi-trait indices as well as investment in genetic technologies should significantly increase potential milk production per hectare. Decades of research on the use of feeds other than pasture (i.e., supplementary feeds) have provided consistent milk production responses when the reduction in pasture intake associated with the provision of supplementary feed (i.e., substitution rate) is accounted for. A unique feature of grazing systems research over the last 70 yr has been the use of multi-year farm systems experimentation. These studies have allowed the evaluation of strategic changes to a component of the system on all the interacting features of the system. This technique has allowed excellent component research to be “systemized” and is an essential part of the development of the intensive grazing production system that exists today. Future challenges include the provision of skilled labor or specifically designed automation to optimize farm management and both environmental sustainability and animal welfare concerns, particularly relating to the concentration of nitrogen in each urine patch and the associated risk of nitrate leaching, as well as concerns regarding exposure of animals to harsh climatic conditions. These combined challenges could affect farmers' “social license” to farm in the future

    Targeting BMI-1 to deplete antibody-secreting cells in autoimmunity

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    Objectives. B cells drive the production of autoreactive antibodysecreting cells, ASCs, in autoimmune diseases such as Systemic Lupus Erythematosus, SLE, and Sjogren, s syndrome, causing long-, term organ damage. Current treatments for antibody-mediated autoimmune diseases target B cells or broadly suppress the immune system. However, pre-existing long-lived ASCs are often refractory to treatment, leaving a reservoir of autoreactive cells that continue to produce antibodies. Therefore, the development of novel treatment methods targeting ASCs is vital to improve patient outcomes. Our objective was to test whether targeting the epigenetic regulator BMI-, could deplete ASCs in autoimmune conditions in vivo and in vitro. Methods. Use of a BMI-, inhibitor in both mouse and human autoimmune settings was investigated. Lyn, mice, a model of SLE, were treated with the BMI-, small molecule inhibitor PTC-, before assessment of ASCs, serum antibody and immune complexes. To examine human ASC survival, a novel human fibroblast-based assay was established, and the impact of PTC-, on ASCs derived from Sjogren, s syndrome, patients was evaluated. Results. BMI-, inhibition significantly decreased splenic and bone marrow ASCs in Lyn, mice. The decline in ASCs was linked to aberrant cell cycle gene expression and led to a significant decrease in serum IgG, immune complexes and anti-DNA IgG. PTC-, was also efficacious in reducing ex vivo plasma cell survival from both Sjogren, s syndrome, patients and age-matched healthy donors. Conclusion. These data provide evidence that inhibiting BMI-, can deplete ASC in a variety of contexts and thus BMI-, is a viable therapeutic target for antibody-mediated autoimmune diseases.Jack Polmear, Lauren Hailes, Moshe Olshansky, Maureen Rischmueller, Elan L'Estrange-Stranieri, Anne L Fletcher, Margaret L Hibbs, Vanessa L Bryant, Kim L Good-Jacobso

    An incremental modular technique for checking LTL-X properties on Petri nets

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    Model-checking is a powerful and widespread technique for the verification of finite state concurrent systems. However, the main hindrance for wider application of this technique is the well-known state explosion problem. Modular verification is a promising natural approach to tackle this problem. It is based on the "divide and conquer" principle and aims at deducing the properties of the system from those of its components analysed in isolation. Unfortunately, several issues make the use of modular verification techniques difficult in practice. First, deciding how to partition the system into components is not trivial and can have a significant impact on the resources needed for verification. Second, when model-checking a component in isolation, how should the environment of this component be described? In this paper, we address these problems in the framework of model-checking LTL\X action-based properties on Petri nets. We propose an incremental and modular verification approach where the system model is partitioned according to the actions occurring in the property to be verified and where the environment of a component is taken into account using the linear place invariants of the system

    Genome-wide DNA methylation analysis of KRAS mutant cell lines

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    Oncogenic RAS mutations are associated with DNA methylation changes that alter gene expression to drive cancer. Recent studies suggest that DNA methylation changes may be stochastic in nature, while other groups propose distinct signaling pathways responsible for aberrant methylation. Better understanding of DNA methylation events associated with oncogenic KRAS expression could enhance therapeutic approaches. Here we analyzed the basal CpG methylation of 11 KRAS-mutant and dependent pancreatic cancer cell lines and observed strikingly similar methylation patterns. KRAS knockdown resulted in unique methylation changes with limited overlap between each cell line. In KRAS-mutant Pa16C pancreatic cancer cells, while KRAS knockdown resulted in over 8,000 differentially methylated (DM) CpGs, treatment with the ERK1/2-selective inhibitor SCH772984 showed less than 40 DM CpGs, suggesting that ERK is not a broadly active driver of KRAS-associated DNA methylation. KRAS G12V overexpression in an isogenic lung model reveals >50,600 DM CpGs compared to non-transformed controls. In lung and pancreatic cells, gene ontology analyses of DM promoters show an enrichment for genes involved in differentiation and development. Taken all together, KRAS-mediated DNA methylation are stochastic and independent of canonical downstream effector signaling. These epigenetically altered genes associated with KRAS expression could represent potential therapeutic targets in KRAS-driven cancer

    A population study of prolonged grief in refugees

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    Published online by Cambridge University Press: 19 August 2019AIMS:Despite the frequency that refugees suffer bereavement, there is a dearth of research into the prevalence and predictors of problematic grief reactions in refugees. To address this gap, this study reports a nationally representative population-based study of refugees to determine the prevalence of probable prolonged grief disorder (PGD) and its associated problems. METHODS:This study recruited participants from the Building a New Life in Australia (BNLA) prospective cohort study of refugees admitted to Australia between October 2013 and February 2014. The current data were collected in 2015-2016, and comprised 1767 adults, as well as 411 children of the adult respondents. Adult refugees were assessed for trauma history, post-migration difficulties, probable PGD, post-traumatic stress disorder (PTSD) and mental illness. Children were administered the Strengths and Difficulties Questionnaire. RESULTS:In this cohort, 38.1% of refugees reported bereavement, of whom 15.8% reported probable PGD; this represents 6.0% of the entire cohort. Probable PGD was associated with a greater likelihood of mental illness, probable PTSD, severe mental illness, currently unemployed and reported disability. Children of refugees with probable PGD reported more psychological difficulties than those whose parents did not have probable PGD. Probable PGD was also associated with the history of imprisonment, torture and separation from family. Only 56.3% of refugees with probable PGD had received psychological assistance. CONCLUSIONS:Bereavement and probable PGD appear highly prevalent in refugees, and PGD seems to be associated with disability in the refugees and psychological problems in their children. The low rate of access to mental health assistance for these refugees highlights that there is a need to address this issue in refugee populations.R. A. Bryant, B. Edwards, M. Creamer, M. O'Donnell, D. Forbes, K. L. Felmingham ... et al
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