2,263 research outputs found

    Locational relations in Yagua narrative

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    From the introduction: In this paper I will attempt to show that locational relations are specified by rhetorical predicates in the same way as the other relations mentioned above are. I suggest that the paucity of locational and directional relations in lists of rhetorical predicates in previous work is due to the absence of specific morphosyntactic devises for indicating such relations in the languages that most linguists speak

    Referential distance and discourse structure in Yagua

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    From the introduction: This paper concerns Yagua, a lowland language of Peru. It also concerns the choices speakers make as to how they will refer to or code participants in discourse. The body of this paper will be organized into two broad parts corresponding to these two most general concerns. In the first part, consisting of Sect. 2, I will describe the major formal devices used to code participants in Yagua. In the second part, Sect. 3 and 4, I will look at the use of those devices in a body of folkloric narrative texts. I will take as a starting point for the textual study the framework and methodology developed by Givón (1983a, b, c, d) for measuring referential distance , i.e., the distance in number of clauses between one mention of a participant and its previous mention in the text. The general framework is outlined in some depth and several substantive modifications to the methodology are proposed. Deviations from the general predictions of Givón\u27s framework will then be examined in detail in Sect. 4. It is found that there are two circumstances under which relatively new participants can be coded with attenuated coding devices (i.e., verb coding and enclitics), and seven circumstances under which relatively recently mentioned participants can be coded with full noun phrases. Each of these circumstances represents an area of further research into the functional factors underlying the choice of participant coding devices in discourse

    How much does smoking cessation cut CHD risk?

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    Patients with coronary heart disease (CHD) who refrain from smoking over a 2-year follow-up period decrease their relative risk (RR) for morbidity and mortality by about one third (strength of recommendation [SOR]: A, meta-analysis of 20 cohort studies). People who maintain abstinence after coronary artery bypass surgery are more likely to avoid angina, repeat revascularization, significant physical impairment, and CHD-related hospital admissions than patients who continue to smoke (SOR: A, 4 cohort studies with 1- to 20-year follow-up)

    A novel FRET-based screen in high-throughput format to identify inhibitors of malarial and human glucose transporters

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    The glucose transporter PfHT is essential to the survival of the malaria parasite Plasmodium falciparum and has been shown to be a druggable target with high potential for pharmacological intervention. Identification of compounds against novel drug targets is crucial to combating resistance against current therapeutics. Here, we describe the development of a cell-based assay system readily adaptable to high-throughput screening that directly measures compound effects on PfHT-mediated glucose transport. Intracellular glucose concentrations are detected using a genetically encoded fluorescence resonance energy transfer (FRET)-based glucose sensor. This allows assessment of the ability of small molecules to inhibit glucose uptake with high accuracy (Z′ factor of >0.8), thereby eliminating the need for radiolabeled substrates. Furthermore, we have adapted this assay to counterscreen PfHT hits against the human orthologues GLUT1, -2, -3, and -4. We report the identification of several hits after screening the Medicines for Malaria Venture (MMV) Malaria Box, a library of 400 compounds known to inhibit erythrocytic development of P. falciparum. Hit compounds were characterized by determining the half-maximal inhibitory concentration (IC(50)) for the uptake of radiolabeled glucose into isolated P. falciparum parasites. One of our hits, compound MMV009085, shows high potency and orthologue selectivity, thereby successfully validating our assay for antimalarial screening

    Low-Voltage Polymer/Small-Molecule Blend Organic Thin-Film Transistors and Circuits Fabricated via Spray Deposition

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    Organic thin-film electronics have long been considered an enticing candidate in achieving high-throughput manufacturing of low-power ubiquitous electronics. However, to achieve this goal, more work is required to reduce operating voltages and develop suitable mass-manufacture techniques. Here, we demonstrate low-voltage spray-cast organic thin-film transistors based on a semiconductor blend of 2,8-difluoro- 5,11-bis (triethylsilylethynyl) anthradithiophene and poly(triarylamine). Both semiconductor and dielectric films are deposited via successive spray deposition in ambient conditions (air with 40%–60% relative humidity) without any special precautions. Despite the simplicity of the deposition method, p-channel transistors with hole mobilities of \u3e1 cm2/Vs are realized at −4 V operation, and unipolar inverters operating at −6 V are demonstrated

    Transmission dynamics: Data sharing in the COVID-19 era

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    Problem: The current coronavirus disease 2019 (COVID-19) pandemic underscores the need for building and sustaining public health data infrastructure to support a rapid local, regional, national, and international response. Despite a historical context of public health crises, data sharing agreements and transactional standards do not uniformly exist between institutions which hamper a foundational infrastructure to meet data sharing and integration needs for the advancement of public health. Approach: There is a growing need to apply population health knowledge with technological solutions to data transfer, integration, and reasoning, to improve health in a broader learning health system ecosystem. To achieve this, data must be combined from healthcare provider organizations, public health departments, and other settings. Public health entities are in a unique position to consume these data, however, most do not yet have the infrastructure required to integrate data sources and apply computable knowledge to combat this pandemic. Outcomes: Herein, we describe lessons learned and a framework to address these needs, which focus on: (a) identifying and filling technology gaps ; (b) pursuing collaborative design of data sharing requirements and transmission mechanisms; (c) facilitating cross-domain discussions involving legal and research compliance; and (d) establishing or participating in multi-institutional convening or coordinating activities. Next steps: While by no means a comprehensive evaluation of such issues, we envision that many of our experiences are universal. We hope those elucidated can serve as the catalyst for a robust community-wide dialogue on what steps can and should be taken to ensure that our regional and national health care systems can truly learn, in a rapid manner, so as to respond to this and future emergent public health crises

    Real-time insight into the multistage mechanism of nanoparticle exsolution from a perovskite host surface

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    In exsolution, nanoparticles form by emerging from oxide hosts by application of redox driving forces, leading to transformative advances in stability, activity, and efficiency over deposition techniques, and resulting in a wide range of new opportunities for catalytic, energy and net-zero-related technologies. However, the mechanism of exsolved nanoparticle nucleation and perovskite structural evolution, has, to date, remained unclear. Herein, we shed light on this elusive process by following in real time Ir nanoparticle emergence from a SrTiO3 host oxide lattice, using in situ high-resolution electron microscopy in combination with computational simulations and machine learning analytics. We show that nucleation occurs via atom clustering, in tandem with host evolution, revealing the participation of surface defects and host lattice restructuring in trapping Ir atoms to initiate nanoparticle formation and growth. These insights provide a theoretical platform and practical recommendations to further the development of highly functional and broadly applicable exsolvable materials

    Nicotiana alata defensin chimeras reveal differences in the mechanism of fungal and tumor cell killing and an enhanced antifungal variant

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    The plant defensin NaD1 is a potent antifungal molecule that also targets tumor cells with a high efficiency. We examined the features of NaD1 that contribute to these two activities by producing a series of chimeras with NaD2, a defensin that has relatively poor activity against fungi and no activity against tumor cells. All plant defensins have a common tertiary structure known as a cysteine-stabilized alpha-beta motif which consists of an alpha helix and a triple-stranded beta-sheet stabilized by four disulfide bonds. The chimeras were produced by replacing loops 1 to 7, the sequences between each of the conserved cysteine residues on NaD1, with the corresponding loops from NaD2. The loop 5 swap replaced the sequence motif (SKILRR) that mediates tight binding with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2] and is essential for the potent cytotoxic effect of NaD1 on tumor cells. Consistent with previous reports, there was a strong correlation between PI(4,5)P-2 binding and the tumor cell killing activity of all of the chimeras. However, this correlation did not extend to antifungal activity. Some of the loop swap chimeras were efficient antifungal molecules, even though they bound poorly to PI(4,5)P-2, suggesting that additional mechanisms operate against fungal cells. Unexpectedly, the loop 1B swap chimera was 10 times more active than NaD1 against filamentous fungi. This led to the conclusion that defensin loops have evolved as modular components that combine to make antifungal molecules with variable mechanisms of action and that artificial combinations of loops can increase antifungal activity compared to that of the natural variants

    Narratives to enhance smoking cessation interventions among African-American smokers, the ACCE project

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    BACKGROUND: Low-income, African-American smokers are less likely to have resources to aid in quitting smoking. Narrative communication may provide an enhancement to traditional smoking cessation interventions like NRT, medications, or behavioral treatments for this audience. After extensive pilot testing of stories and personal experiences with smoking cessation from African-Americans from a low-income community, we conducted a randomized control trial using stories to augment routine inpatient treatment among African-Americans at an urban Southern hospital (N = 300). RESULTS: Differences in smoking cessation outcomes between the intervention (stories DVD + routine clinical treatment) and control (routine clinical treatment) arms were compared using self-report and carbon monoxide measurement at 6-months. Compared to control, individuals who viewed the intervention stories DVD reported greater intentions to quit. Although continuous quitting marginally favored the intervention, our main result did not reach statistical significance (p = 0.16). CONCLUSION: Narrative communication via storytelling to promote smoking cessation among African-Americans in the South is one method to communicate smoking cessation. Results suggest this may not be sufficient as a stand-alone augmentation of routine clinical treatment for continuous smoking cessation. Smoking cessation efforts need to continually assess different means of communicating to smokers about quitting. CLINICAL TRIALS REGISTRATION: The ClinicalTrials.gov Identifier is NCT00101491. This trial was registered January 10, 2005

    Patient-Reported Functional Outcomes After Hypofractionated or Conventionally Fractionated Radiation for Prostate Cancer: A National Cohort Study in England.

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    PURPOSE: The aim of the current study was to determine patient-reported functional outcomes in men with prostate cancer (PCa) undergoing moderately hypofractionated (H-RT) or conventionally fractionated radiation therapy (C-RT) in a national cohort study. PATIENDS AND METHODS: All men diagnosed with PCa between April 2014 and September 2016 in the English National Health Service undergoing C-RT or H-RT were identified in the National Prostate Cancer Audit and mailed a questionnaire at least 18 months after diagnosis. We estimated differences in patient-reported urinary, bowel, sexual, and hormonal function-Expanded Prostate Cancer Index Composite short-form 26 domain scores on a 0 to 100 scale-and health-related quality of life-EQ-5D-5L on a 0 to 1 scale-using linear regression with adjustment for patient, tumor, and treatment-related factors in addition to GI and genitourinary baseline function, with higher scores representing better outcomes. RESULTS: Of the 17,058 men in the cohort, 77% responded: 8,432 men received C-RT (64.2%) and 4,699 H-RT (35.8%). Men in the H-RT group were older (age ≥ 70 years: 67.5% v 60.9%), fewer men had locally advanced disease (56.5% v 71.3%), were less likely to receive androgen-deprivation therapy (79.5% v 87.8%), and slightly more men had pretreatment genitourinary procedures (24.2% v 21.2%). H-RT was associated with small increases in adjusted mean Expanded Prostate Cancer Index Composite short-form 26 sexual (3.3 points; 95% CI, 2.1 to 4.5; P < .001) and hormonal function scores (3.2 points; 95% CI, 1.8 to 4.6; P < .001). These differences failed to meet established thresholds for a clinically meaningful change. There were no statistically significant differences in urinary or bowel function and quality of life. CONCLUSION: This is the first national cohort study comparing functional outcomes after H-RT and C-RT reported by patients. These real-world results further support the use of H-RT as the standard for radiation therapy in men with nonmetastatic PCa
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