785 research outputs found

    How Do UX Practitioners Communicate AI as a Design Material? Artifacts, Conceptions, and Propositions

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    UX practitioners (UXPs) face novel challenges when working with and communicating artificial intelligence (AI) as a design material. We explore how UXPs communicate AI concepts when given hands-on experience training and experimenting with AI models. To do so, we conducted a task-based design study with 27 UXPs in which they prototyped and created a design presentation for a AI-enabled interface while having access to a simple AI model training tool. Through analyzing UXPs' design presentations and post-activity interviews, we found that although UXPs struggled to clearly communicate some AI concepts, tinkering with AI broadened common ground when communicating with technical stakeholders. UXPs also identified key risks and benefits of AI in their designs, and proposed concrete next steps for both UX and AI work. We conclude with a sensitizing concept and recommendations for design and AI tools to enhance multi-stakeholder communication and collaboration when crafting human-centered AI experiences

    Examining the Impact of Provenance-Enabled Media on Trust and Accuracy Perceptions

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    In recent years, industry leaders and researchers have proposed to use technical provenance standards to address visual misinformation spread through digitally altered media. By adding immutable and secure provenance information such as authorship and edit date to media metadata, social media users could potentially better assess the validity of the media they encounter. However, it is unclear how end users would respond to provenance information, or how to best design provenance indicators to be understandable to laypeople. We conducted an online experiment with 595 participants from the US and UK to investigate how provenance information altered users' accuracy perceptions and trust in visual content shared on social media. We found that provenance information often lowered trust and caused users to doubt deceptive media, particularly when it revealed that the media was composited. We additionally tested conditions where the provenance information itself was shown to be incomplete or invalid, and found that these states have a significant impact on participants' accuracy perceptions and trust in media, leading them, in some cases, to disbelieve honest media. Our findings show that provenance, although enlightening, is still not a concept well-understood by users, who confuse media credibility with the orthogonal (albeit related) concept of provenance credibility. We discuss how design choices may contribute to provenance (mis)understanding, and conclude with implications for usable provenance systems, including clearer interfaces and user education.Comment: Accepted to CSCW 202

    Regulation of α5β1 integrin conformation and function by urokinase receptor binding

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    Urokinase-type plasminogen activator receptors (uPARs), up-regulated during tumor progression, associate with β1 integrins, localizing urokinase to sites of cell attachment. Binding of uPAR to the β-propeller of α3β1 empowers vitronectin adhesion by this integrin. How uPAR modifies other β1 integrins remains unknown. Using recombinant proteins, we found uPAR directly binds α5β1 and rather than blocking, renders fibronectin (Fn) binding by α5β1 Arg-Gly-Asp (RGD) resistant. This resulted from RGD-independent binding of α5β1–uPAR to Fn type III repeats 12–15 in addition to type III repeats 9–11 bound by α5β1. Suppression of endogenous uPAR by small interfering RNA in tumor cells promoted weaker, RGD-sensitive Fn adhesion and altered overall α5β1 conformation. A β1 peptide (res 224NLDSPEGGF232) that models near the known α-chain uPAR-binding region, or a β1-chain Ser227Ala point mutation, abrogated effects of uPAR on α5β1. Direct binding and regulation of α5β1 by uPAR implies a modified “bent” integrin conformation can function in an alternative activation state with this and possibly other cis-acting membrane ligands

    Exoplanet phase curves: observations and theory

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    Phase curves are the best technique to probe the three dimensional structure of exoplanets' atmospheres. In this chapter we first review current exoplanets phase curve observations and the particular challenges they face. We then describe the different physical mechanisms shaping the atmospheric phase curves of highly irradiated tidally locked exoplanets. Finally, we discuss the potential for future missions to further advance our understanding of these new worlds.Comment: Fig.5 has been updated. Table 1 and corresponding figures have been updated with new values for WASP-103b and WASP-18b. Contains a table sumarizing phase curve observation

    Predictors of Nodal and Metastatic Failure in Early Stage Non-Small Cell Lung Cancer after Stereotactic Body Radiation Therapy

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    Introduction/Background Many early-stage non-small cell lung cancer (ES-NSCLC) patients undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. Materials and Methods We included 363 patients with ES-NSCLC who received SBRT; median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): sex; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. Results A total of 111/406 (27.3%) lesions metastasized. GTV volume and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (p<0.001 and HR=1.02 per mL, p<0.05 and HR=0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV volume and prescription dose was built: [risk score=(0.01611 x GTV)–(0.00525 x dose (BED10))]. Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk-score identified significant differences in time to metastases between low-, medium-, and high-risk patients (p<0.001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. Conclusion GTV volume and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT

    Successful Genetic Transfection of the Colonic Protistan Parasite Blastocystis for Reliable Expression of Ectopic Genes

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    The microbial parasite Blastocystis colonizes the large intestines of numerous animal species and increasing evidence has linked Blastocystis infection to enteric diseases with signs and symptoms including abdominal pain, constipation, diarrhea, nausea, vomiting, and flatulence. It has also recently been reported to be an important member of the host intestinal microbiota. Despite significant advances in our understanding of Blastocystis cell biology and host-parasite interactions, a genetic modification tool is absent. In this study, we successfully established a robust gene delivery protocol for Blastocystis subtype 7 (ST7) and ectopic protein expression was further tested using a high sensitivity nano-luciferase (Nluc) reporter system, with promoter regions from several genes. Among them, a strong promoter encompassing a region upstream of the legumain 5? UTR was identified. Using this promoter combined with the legumain 3? UTR, which contains a conserved, precise polyadenylation signal, a robust transient transfection technique was established for the first time in Blastocystis. This system was validated by ectopic expression of proteins harbouring specific localization signals. The establishment of a robust, reproducible gene modification system for Blastocystis is a significant advance for Blastocystis research both in vitro and in vivo. This technique will spearhead further research to understand the parasite’s biology, its role in health and disease, along with novel ways to combat the parasite

    Single-mode instability in standing-wave lasers: The quantum cascade laser as a self-pumped parametric oscillator

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    We report the observation of a clear single-mode instability threshold in continuous-wave Fabry-Perot quantum cascade lasers (QCLs). The instability is characterized by the appearance of sidebands separated by tens of free spectral ranges (FSR) from the first lasing mode, at a pump current not much higher than the lasing threshold. As the current is increased, higher-order sidebands appear that preserve the initial spacing, and the spectra are suggestive of harmonically phase-locked waveforms. We present a theory of the instability that applies to all homogeneously broadened standing-wave lasers. The low instability threshold and the large sideband spacing can be explained by the combination of an unclamped, incoherent Lorentzian gain due to the population grating, and a coherent parametric gain caused by temporal population pulsations that changes the spectral gain line shape. The parametric term suppresses the gain of sidebands whose separation is much smaller than the reciprocal gain recovery time, while enhancing the gain of more distant sidebands. The large gain recovery frequency of the QCL compared to the FSR is essential to observe this parametric effect, which is responsible for the multiple-FSR sideband separation. We predict that by tuning the strength of the incoherent gain contribution, for example by engineering the modal overlap factors and the carrier diffusion, both amplitude-modulated (AM) or frequency-modulated emission can be achieved from QCLs. We provide initial evidence of an AM waveform emitted by a QCL with highly asymmetric facet reflectivities, thereby opening a promising route to ultrashort pulse generation in the mid-infrared. Together, the experiments and theory clarify a deep connection between parametric oscillation in optically pumped microresonators and the single-mode instability of lasers, tying together literature from the last 60 years.United States. Defense Advanced Research Projects Agency. Spectral Combs from UV to THz Program (Grant W31P4Q-16-1-0002)National Science Foundation (U.S.) (Awards ECCS-1230477, ECCS-1614631 and ECCS- 1614531)United States. Dept. of Defense. Assistant Secretary of Defense for Research & Engineering (Air Force Contracts FA8721-05-C- 0002 and No. FA8702-15-D-0001

    Gaugino Anomaly Mediated SUSY Breaking: phenomenology and prospects for the LHC

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    We examine the supersymmetry phenomenology of a novel scenario of supersymmetry (SUSY) breaking which we call Gaugino Anomaly Mediation, or inoAMSB. This is suggested by recent work on the phenomenology of flux compactified type IIB string theory. The essential features of this scenario are that the gaugino masses are of the anomaly-mediated SUSY breaking (AMSB) form, while scalar and trilinear soft SUSY breaking terms are highly suppressed. Renormalization group effects yield an allowable sparticle mass spectrum, while at the same time avoiding charged LSPs; the latter are common in models with negligible soft scalar masses, such as no-scale or gaugino mediation models. Since scalar and trilinear soft terms are highly suppressed, the SUSY induced flavor and CP-violating processes are also suppressed. The lightest SUSY particle is the neutral wino, while the heaviest is the gluino. In this model, there should be a strong multi-jet +etmiss signal from squark pair production at the LHC. We find a 100 fb^{-1} reach of LHC out to m_{3/2}\sim 118 TeV, corresponding to a gluino mass of \sim 2.6 TeV. A double mass edge from the opposite-sign/same flavor dilepton invariant mass distribution should be visible at LHC; this, along with the presence of short-- but visible-- highly ionizing tracks from quasi-stable charginos, should provide a smoking gun signature for inoAMSB.Comment: 30 pages including 14 .eps figure

    Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study

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    BACKGROUND: The standard of care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is typically preceded by neoadjuvant chemotherapy. However, the inability to assess minimal residual disease (MRD) noninvasively limits our ability to offer bladder-sparing treatment. Here, we sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis. METHODS AND FINDINGS: We applied urine Cancer Personalized Profiling by Deep Sequencing (uCAPP-Seq), a targeted next-generation sequencing (NGS) method for detecting utDNA, to urine cell-free DNA (cfDNA) samples acquired between April 2019 and November 2020 on the day of curative-intent radical cystectomy from 42 patients with localized bladder cancer. The average age of patients was 69 years (range: 50 to 86), of whom 76% (32/42) were male, 64% (27/42) were smokers, and 76% (32/42) had a confirmed diagnosis of MIBC. Among MIBC patients, 59% (19/32) received neoadjuvant chemotherapy. utDNA variant calling was performed noninvasively without prior sequencing of tumor tissue. The overall utDNA level for each patient was represented by the non-silent mutation with the highest variant allele fraction after removing germline variants. Urine was similarly analyzed from 15 healthy adults. utDNA analysis revealed a median utDNA level of 0% in healthy adults and 2.4% in bladder cancer patients. When patients were classified as those who had residual disease detected in their surgical sample (n = 16) compared to those who achieved a pathologic complete response (pCR; n = 26), median utDNA levels were 4.3% vs. 0%, respectively (p = 0.002). Using an optimal utDNA threshold to define MRD detection, positive utDNA MRD detection was highly correlated with the absence of pCR (p \u3c 0.001) with a sensitivity of 81% and specificity of 81%. Leave-one-out cross-validation applied to the prediction of pathologic response based on utDNA MRD detection in our cohort yielded a highly significant accuracy of 81% (p = 0.007). Moreover, utDNA MRD-positive patients exhibited significantly worse progression-free survival (PFS; HR = 7.4; 95% CI: 1.4-38.9; p = 0.02) compared to utDNA MRD-negative patients. Concordance between urine- and tumor-derived mutations, determined in 5 MIBC patients, was 85%. Tumor mutational burden (TMB) in utDNA MRD-positive patients was inferred from the number of non-silent mutations detected in urine cfDNA by applying a linear relationship derived from The Cancer Genome Atlas (TCGA) whole exome sequencing of 409 MIBC tumors. We suggest that about 58% of these patients with high inferred TMB might have been candidates for treatment with early immune checkpoint blockade. Study limitations included an analysis restricted only to single-nucleotide variants (SNVs), survival differences diminished by surgery, and a low number of DNA damage response (DRR) mutations detected after neoadjuvant chemotherapy at the MRD time point. CONCLUSIONS: utDNA MRD detection prior to curative-intent radical cystectomy for bladder cancer correlated significantly with pathologic response, which may help select patients for bladder-sparing treatment. utDNA MRD detection also correlated significantly with PFS. Furthermore, utDNA can be used to noninvasively infer TMB, which could facilitate personalized immunotherapy for bladder cancer in the future

    Genetic risk variants for social anxiety

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136300/1/ajmgb32520.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136300/2/ajmgb32520_am.pd
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