2,061 research outputs found
Trolleys, crashes, and perception - a survey on how current autonomous vehicles debates invoke problematic expectations
Ongoing debates about ethical guidelines for autonomous vehicles mostly focus on variations of the ‘Trolley Problem’. Using variations of this ethical dilemma in preference surveys, possible implications for autonomous vehicles policy are discussed. In this work, we argue that the lack of realism in such scenarios leads to limited practical insights. We run an ethical preference survey for autonomous vehicles by including more realistic features, such as time pressure and a non-binary decision option. Our results indicate that such changes lead to different outcomes, calling into question how the current outcomes can be generalized. Additionally, we investigate the framing effects of the capabilities of autonomous vehicles and indicate that ongoing debates need to set realistic expectations on autonomous vehicle challenges. Based on our results, we call upon the field to re-frame the current debate towards more realistic discussions beyond the Trolley Problem and focus on which autonomous vehicle behavior is considered not to be acceptable, since a consensus on what the right solution is, is not reachable
Ultrasound IMT measurement on a multi-ethnic and multi-institutional database: Our review and experience using four fully automated and one semi-automated methods
Automated and high performance carotid intima-media thickness (IMT) measurement is gaining increasing importance in clinical practice to assess the cardiovascular risk of patients. In this paper, we compare four fully automated IMT measurement techniques (CALEX, CAMES, CARES and CAUDLES) and one semi-automated technique (FOAM). We present our experience using these algorithms, whose lumen-intima and media-adventitia border estimation use different methods that can be: (a) edge-based; (b) training-based; (c) feature-based; or (d) directional Edge-Flow based. Our database (DB) consisted of 665 images that represented a multi-ethnic group and was acquired using four OEM scanners. The performance evaluation protocol adopted error measures, reproducibility measures, and Figure of Merit (FoM). FOAM showed the best performance, with an IMT bias equal to 0.025 ± 0.225 mm, and a FoM equal to 96.6%. Among the four automated methods, CARES showed the best results with a bias of 0.032 ± 0.279 mm, and a FoM to 95.6%, which was statistically comparable to that of FOAM performance in terms of accuracy and reproducibility. This is the first time that completely automated and user-driven techniques have been compared on a multi-ethnic dataset, acquired using multiple original equipment manufacturer (OEM) machines with different gain settings, representing normal and pathologic case
Adaptive Variation Regulates the Expression of the Human SGK1 Gene in Response to Stress
The Serum and Glucocorticoid-regulated Kinase1 (SGK1) gene is a target of the glucocorticoid receptor (GR) and is central to the stress response in many human tissues. Because environmental stress varies across habitats, we hypothesized that natural selection shaped the geographic distribution of genetic variants regulating the level of SGK1 expression following GR activation. By combining population genetics and molecular biology methods, we identified a variant (rs9493857) with marked allele frequency differences between populations of African and European ancestry and with a strong correlation between allele frequency and latitude in worldwide population samples. This SNP is located in a GR-binding region upstream of SGK1 that was identified using a GR ChIP-chip. SNP rs9493857 also lies within a predicted binding site for Oct1, a transcription factor known to cooperate with the GR in the transactivation of target genes. Using ChIP assays, we show that both GR and Oct1 bind to this region and that the ancestral allele at rs9493857 binds the GR-Oct1 complex more efficiently than the derived allele. Finally, using a reporter gene assay, we demonstrate that the ancestral allele is associated with increased glucocorticoid-dependent gene expression when compared to the derived allele. Our results suggest a novel paradigm in which hormonal responsiveness is modulated by sequence variation in the regulatory regions of nuclear receptor target genes. Identifying such functional variants may shed light on the mechanisms underlying inter-individual variation in response to environmental stressors and to hormonal therapy, as well as in the susceptibility to hormone-dependent diseases
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Adaptive Variation Regulates the Expression of the Human <i>SGK1</i> Gene in Response to Stress
The Serum and Glucocorticoid-regulated Kinase1 (SGK1) gene is a target of the glucocorticoid receptor (GR) and is central to the stress response in many human tissues. Because environmental stress varies across habitats, we hypothesized that natural selection shaped the geographic distribution of genetic variants regulating the level of SGK1 expression following GR activation. By combining population genetics and molecular biology methods, we identified a variant (rs9493857) with marked allele frequency differences between populations of African and European ancestry and with a strong correlation between allele frequency and latitude in worldwide population samples. This SNP is located in a GR-binding region upstream of SGK1 that was identified using a GR ChIP-chip. SNP rs9493857 also lies within a predicted binding site for Oct1, a transcription factor known to cooperate with the GR in the transactivation of target genes. Using ChIP assays, we show that both GR and Oct1 bind to this region and that the ancestral allele at rs9493857 binds the GR-Oct1 complex more efficiently than the derived allele. Finally, using a reporter gene assay, we demonstrate that the ancestral allele is associated with increased glucocorticoid-dependent gene expression when compared to the derived allele. Our results suggest a novel paradigm in which hormonal responsiveness is modulated by sequence variation in the regulatory regions of nuclear receptor target genes. Identifying such functional variants may shed light on the mechanisms underlying inter-individual variation in response to environmental stressors and to hormonal therapy, as well as in the susceptibility to hormone-dependent diseases.</p
A Ferroelectric Tunnel Junction-based Integrate-and-Fire Neuron
Event-based neuromorphic systems provide a low-power solution by using
artificial neurons and synapses to process data asynchronously in the form of
spikes. Ferroelectric Tunnel Junctions (FTJs) are ultra low-power memory
devices and are well-suited to be integrated in these systems. Here, we present
a hybrid FTJ-CMOS Integrate-and-Fire neuron which constitutes a fundamental
building block for new-generation neuromorphic networks for edge computing. We
demonstrate electrically tunable neural dynamics achievable by tuning the
switching of the FTJ device
The applicability of FIR fine-structure lines as Star Formation Rate tracers over wide ranges of metallicities and galaxy types
We analyze the applicability of far-infrared fine-structure lines [CII] 158
micron, [OI] 63 micron and [OIII] 88 micron to reliably trace the star
formation rate (SFR) in a sample of low-metallicity dwarf galaxies from the
Herschel Dwarf Galaxy Survey and compare with a broad sample of galaxies of
various types and metallicities in the literature. We study the trends and
scatter in the relation between the SFR (as traced by GALEX FUV and MIPS 24
micron) and far-infrared line emission, on spatially resolved and global galaxy
scales, in dwarf galaxies. We assemble far-infrared line measurements from the
literature and infer whether the far-infrared lines can probe the SFR (as
traced by the total-infrared luminosity) in a variety of galaxy populations. In
metal-poor dwarfs, the [OI] and [OIII] lines show the strongest correlation
with the SFR with an uncertainty on the SFR estimates better than a factor of
2, while the link between [CII] emission and the SFR is more dispersed
(uncertainty factor of 2.6). The increased scatter in the SFR-L([CII]) relation
towards low metal abundances, warm dust temperatures, large filling factors of
diffuse, highly ionized gas suggests that other cooling lines start to dominate
depending on the density and ionization state of the gas. For the literature
sample, we evaluate the correlations for a number of different galaxy
populations. The [CII] and [OI] lines are considered to be reliable SFR tracers
in starburst galaxies, recovering the star formation activity within an
uncertainty of factor 2. [Abridged]Comment: 35 pages, 13 figures, accepted for publication in A&A on May 7th 201
OR13-1 Burosumab Improves the Biochemical, Skeletal, and Clinical Symptoms of Tumor-Induced Osteomalacia Syndrome
Tumor-induced Osteomalacia (TIO) and Epidermal Nevus Syndrome with osteomalacia (ENS) are rare conditions in which ectopic production of FGF23 by tumor (TIO) and bone (ENS) lead to renal phosphate wasting, impaired 1,25(OH)2D synthesis, osteomalacia, fractures, weakness, fatigue and decreased mobility. In an ongoing open-label Phase 2 study (NCT02304367), 17 adults were enrolled and treated with burosumab, a fully human monoclonal antibody against FGF23. Key endpoints were change in serum phosphorus and osteomalacia as assessed from trans-iliac crest bone biopsies. The per protocol (PP) analysis included 14/17 subjects who received 0.3-2.0 mg/kg burosumab every 4 weeks (W). Three subjects were excluded: 1 received subthreshold dosing (0.3 mg/kg at Day 0 and 0.15 mg/kg at W8, W32, and W72); 2 were diagnosed with X-linked hypophosphatemia post-enrollment. Ten subjects in the PP group had paired bone biopsies at baseline and W48. Mean ± SE histomorphometric values for the 8/10 subjects with osteomalacia at baseline were 20.4 ± 4.2 µm for osteoid thickness (OT), 23.0 ± 7.2% for osteoid volume/bone volume (OV/BV), and 66.1 ± 10.6% for osteoid surface/bone surface (OS/BS); baseline median (Q1, Q3) for mineralization lag time (MLT) was 1672 (1102, 2929) days. At W48, histomorphometric indices improved as shown by mean percentage changes in OT (37%), OV/BV (40%), OS/BS (-5%), and MLT (median percentage change -78%). Serum phosphorus, fatigue, and physical functioning are reported for the PP group. Mean (SD) serum phosphorus was 1.5 (0.3) mg/dL at baseline and 2.6 (0.8) mg/dL when averaged across the mid-point of the dose interval through W24. After W24, serum phosphorus, assessed only at the end of the dose interval, maintained this increase through W72. Mean (SD) Global Fatigue Score decreased from 5.3 (2.8) at baseline to 3.6 (2.9) at W48 (p=0.020) and to 3.3 (2.7) at W72 (p=0.004). The SF-36 mean (SD) physical component summary score increased from 34 (11) at baseline to 39 (10) at W48 (p=0.059) and to 42 (10) at W72 (p=0.003). Mean (SD) vitality score increased from 41 (14) to 47 (12) at W48 (p=0.075) and to 49 (12) at W72 (p=0.012). The mean (SD) number of sit-to-stand repetitions increased from 6.9 (4.0) at baseline to 8.6 (4.2) at W48 (n=10; p=0.004). By W72, all 17 subjects had ≥1 adverse event (AE). There were 13 serious AEs in 6 subjects, none were considered drug-related. Tumor progression occurred only in subjects with a history of tumor progression prior to enrollment. One subject discontinued treatment prior to W48 to treat tumor progression with chemotherapy. There was 1 death, considered unrelated to treatment. In adults with TIO Syndrome, burosumab was associated with improvements in serum phosphorus, osteomalacia, mobility, quality of life, and reductions in fatigue
Characterizing the Habitable Zones of Exoplanetary Systems with a Large Ultraviolet/Visible/Near-IR Space Observatory
Understanding the surface and atmospheric conditions of Earth-size, rocky
planets in the habitable zones (HZs) of low-mass stars is currently one of the
greatest astronomical endeavors. Knowledge of the planetary effective surface
temperature alone is insufficient to accurately interpret biosignature gases
when they are observed in the coming decades. The UV stellar spectrum drives
and regulates the upper atmospheric heating and chemistry on Earth-like
planets, is critical to the definition and interpretation of biosignature
gases, and may even produce false-positives in our search for biologic
activity. This white paper briefly describes the scientific motivation for
panchromatic observations of exoplanetary systems as a whole (star and planet),
argues that a future NASA UV/Vis/near-IR space observatory is well-suited to
carry out this work, and describes technology development goals that can be
achieved in the next decade to support the development of a UV/Vis/near-IR
flagship mission in the 2020s.Comment: Submitted in response to NASA call for white papers: "Large
Astrophysics Missions to Be Studied by NASA Prior to the 2020 Decadal Survey
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