Evorus: A Crowd-powered Conversational Assistant Built to Automate Itself Over Time

Crowd-powered conversational assistants have been shown to be more robust than automated systems, but do so at the cost of higher response latency and monetary costs. A promising direction is to combine the two approaches for high quality, low latency, and low cost solutions. In this paper, we introduce Evorus, a crowd-powered conversational assistant built to automate itself over time by (i) allowing new chatbots to be easily integrated to automate more scenarios, (ii) reusing prior crowd answers, and (iii) learning to automatically approve response candidates. Our 5-month-long deployment with 80 participants and 281 conversations shows that Evorus can automate itself without compromising conversation quality. Crowd-AI architectures have long been proposed as a way to reduce cost and latency for crowd-powered systems; Evorus demonstrates how automation can be introduced successfully in a deployed system. Its architecture allows future researchers to make further innovation on the underlying automated components in the context of a deployed open domain dialog system.Comment: 10 pages. To appear in the Proceedings of the Conference on Human Factors in Computing Systems 2018 (CHI'18

H0LiCOW III. Quantifying the effect of mass along the line of sight to the gravitational lens HE 0435-1223 through weighted galaxy counts

Based on spectroscopy and multiband wide-field observations of the gravitationally lensed quasar HE 0435-1223, we determine the probability distribution function of the external convergence $\kappa_\mathrm{ext}$ for this system. We measure the under/overdensity of the line of sight towards the lens system and compare it to the average line of sight throughout the universe, determined by using the CFHTLenS as a control field. Aiming to constrain $\kappa_\mathrm{ext}$ as tightly as possible, we determine under/overdensities using various combinations of relevant informative weighing schemes for the galaxy counts, such as projected distance to the lens, redshift, and stellar mass. We then convert the measured under/overdensities into a $\kappa_\mathrm{ext}$ distribution, using ray-tracing through the Millennium Simulation. We explore several limiting magnitudes and apertures, and account for systematic and statistical uncertainties relevant to the quality of the observational data, which we further test through simulations. Our most robust estimate of $\kappa_\mathrm{ext}$ has a median value $\kappa^\mathrm{med}_\mathrm{ext} = 0.004$ and a standard deviation of $\sigma_\kappa = 0.025$. The measured $\sigma_\kappa$ corresponds to $2.5\%$ uncertainty on the time delay distance, and hence the Hubble constant $H_0$ inference from this system. The median $\kappa^\mathrm{med}_\mathrm{ext}$ value is robust to $\sim0.005$ (i.e. $\sim0.5\%$ on $H_0$) regardless of the adopted aperture radius, limiting magnitude and weighting scheme, as long as the latter incorporates galaxy number counts, the projected distance to the main lens, and a prior on the external shear obtained from mass modeling. The availability of a well-constrained $\kappa_\mathrm{ext}$ makes \hequad\ a valuable system for measuring cosmological parameters using strong gravitational lens time delays.Comment: 24 pages, 17 figures, 6 tables. Submitted to MNRA

Tree defence and bark beetles in a drying world: carbon partitioning, functioning and modelling.

Drought has promoted large-scale, insect-induced tree mortality in recent years, with severe consequences for ecosystem function, atmospheric processes, sustainable resources and global biogeochemical cycles. However, the physiological linkages among drought, tree defences, and insect outbreaks are still uncertain, hindering our ability to accurately predict tree mortality under on-going climate change. Here we propose an interdisciplinary research agenda for addressing these crucial knowledge gaps. Our framework includes field manipulations, laboratory experiments, and modelling of insect and vegetation dynamics, and focuses on how drought affects interactions between conifer trees and bark beetles. We build upon existing theory and examine several key assumptions: (1) there is a trade-off in tree carbon investment between primary and secondary metabolites (e.g. growth vs defence); (2) secondary metabolites are one of the main component of tree defence against bark beetles and associated microbes; and (3) implementing conifer-bark beetle interactions in current models improves predictions of forest disturbance in a changing climate. Our framework provides guidance for addressing a major shortcoming in current implementations of large-scale vegetation models, the under-representation of insect-induced tree mortality

Thoracoscopic repair of congenital diaphragmatic hernia: two centres’ experience with 60 patients

© 2014, Springer-Verlag Berlin Heidelberg. Methods: All patients who underwent thoracoscopic repair of congenital diaphragmatic hernia between 2010 and 2013 at the two tertiary referral centres were identified. Medical records were retrospectively reviewed. Data including patients’ demographics, peri-operative outcomes, length of hospitalisation and post-operative complications were extracted and analysed. Introduction: Congenital diaphragmatic hernia is a potentially life-threatening neonatal condition which required surgical intervention. With the advances in endosurgical instruments and techniques, thoracoscopic approach is gaining popularity as a standard procedure in the treatment of this condition. In this study, we reviewed our two centres’ experience with thoracoscopic repair of congenital diaphragmatic hernia in recent years. Conclusion: Thoracoscopic repair of congenital diaphragmatic hernia can be performed safely in specialised centres. The post-operative recovery and cosmesis are excellent. Diaphragmatic hernia with large defect remains a challenge for surgeons. Results: 60 patients were identified over the study period, with 46 males and 14 females. 48 patients received operation within the first 7 days of life. There were seven patients with delayed presentation and were operated after 1 month old. The average body weight was 3.03 kg. Left-sided hernia was more prevalent (n = 50). The mean operative time was 88.5 min (range 31–194 min). No conversion to open thoracotomy or laparotomy was required in any of the patients. All patients except one were intubated and paralysed in neonatal intensive care units for at least 3 days after operation. Average hospital stay was 14.6 days. There was no mortality in this series. There were five recurrences, one being the patient without post-operative paralysis, and the others with deficient posterior muscle rim. No musculoskeletal deformity was noted on follow-up examination.postprin

Longitudinal changes in HIV-specific IFN-γ secretion in subjects who received Remune™ vaccination prior to treatment interruption

BACKGROUND: Despite the benefits of highly active antitretroviral therapy (HAART) for suppressing viral replication in HIV infection, virus persists and rebounds during treatment interruption (TI). This study explored whether HAART intensification with Remune™ vaccination before TI can boost HIV-1-specific immunity, leading to improved control of viremia off HAART. METHODS: Ten chronically HIV-infected adults were enrolled in this proof of concept study. After a 6-month HAART intensification phase with didanosine, hydroxyurea, granulocyte-macrophage colony-stimulating factor, (GM-CSF), and a first dose of Remune™ (HIV-1 Immunogen), HAART was discontinued. Patients continued to receive Remune™ every 3 months until the end of study. HAART was restarted if viral load did not fall below 50,000 copies/ml of plasma within 3 months or if CD4+ counts decreased to <200 cells/mm(3). HIV-specific immunity was monitored with the interferon-γ (IFN-γ) ELISPOT assay. RESULTS: All subjects experienced viral rebound during TIs. Although the magnitude and breadth of HIV-specific responses to HLA-restricted optimal peptide panels and Gag p55 peptide pools increased and viral load decreased by 0.44 log(10 )units from TI#1 to TI#2, no significant correlations between these parameters were observed. The patients spent 50.4% of their 36 months follow up off HAART. CONCLUSION: Stopping HAART in this vaccinated population induced immune responses that persisted after therapy was restarted. Induction of HIV-specific immunity beyond IFN-γ secretion may be contributing to better control of viremia during subsequent TIs allowing for long periods off HAART

Estrogen induces global reorganization of chromatin structure in human breast cancer cells

In the cell nucleus, each chromosome is confined to a chromosome territory. This spatial organization of chromosomes plays a crucial role in gene regulation and genome stability. An additional level of organization has been discovered at the chromosome scale: the spatial segregation into open and closed chromatins to form two genome-wide compartments. Although considerable progress has been made in our knowledge of chromatin organization, a fundamental issue remains the understanding of its dynamics, especially in cancer. To address this issue, we performed genome-wide mapping of chromatin interactions (Hi-C) over the time after estrogen stimulation of breast cancer cells. To biologically interpret these interactions, we integrated with estrogen receptor α (ERα) binding events, gene expression and epigenetic marks. We show that gene-rich chromosomes as well as areas of open and highly transcribed chromatins are rearranged to greater spatial proximity, thus enabling genes to share transcriptional machinery and regulatory elements. At a smaller scale, differentially interacting loci are enriched for cancer proliferation and estrogen-related genes. Moreover, these loci are correlated with higher ERα binding events and gene expression. Taken together these results reveal the role of a hormone--estrogen--on genome organization, and its effect on gene regulation in cancer

The Casimir effect as scattering problem

We show that Casimir-force calculations for a finite number of non-overlapping obstacles can be mapped onto quantum-mechanical billiard-type problems which are characterized by the scattering of a fictitious point particle off the very same obstacles. With the help of a modified Krein trace formula the genuine/finite part of the Casimir energy is determined as the energy-weighted integral over the log-determinant of the multi-scattering matrix of the analog billiard problem. The formalism is self-regulating and inherently shows that the Casimir energy is governed by the infrared end of the multi-scattering phase shifts or spectrum of the fluctuating field. The calculation is exact and in principle applicable for any separation(s) between the obstacles. In practice, it is more suited for large- to medium-range separations. We report especially about the Casimir energy of a fluctuating massless scalar field between two spheres or a sphere and a plate under Dirichlet and Neumann boundary conditions. But the formalism can easily be extended to any number of spheres and/or planes in three or arbitrary dimensions, with a variety of boundary conditions or non-overlapping potentials/non-ideal reflectors.Comment: 14 pages, 2 figures, plenary talk at QFEXT07, Leipzig, September 2007, some typos correcte

Pannexin 1 binds β-catenin to modulate melanoma cell growth and metabolism

Melanoma is the most aggressive skin malignancy with increasing incidence worldwide. Pannexin1 (PANX1), a member of the pannexin family of channel-forming glycoproteins, regulates cellular processes in melanoma cells including proliferation, migration, and invasion/metastasis. However, the mechanisms responsible for coordinating and regulating PANX1 function remain unclear. Here, we demonstrated a direct interaction between the C-terminal region of PANX1 and the N-terminal portion of β-catenin, a key transcription factor in the Wnt pathway. At the protein level, β-catenin was significantly decreased when PANX1 was either knocked down or inhibited by two PANX1 blockers, Probenecid and Spironolactone. Immunofluorescence imaging showed a disrupted pattern of β-catenin localization at the cell membrane in PANX1-deficient cells, and transcription of several Wnt target genes, including MITF, was suppressed. In addition, a mitochondrial stress test revealed that the metabolism of PANX1-deficient cells was impaired, indicating a role for PANX1 in the regulation of the melanoma cell metabolic profile. Taken together, our data show that PANX1 directly interacts with β-catenin to modulate growth and metabolism in melanoma cells. These findings provide mechanistic insight into PANX1-mediated melanoma progression and may be applicable to other contexts where PANX1 and β-catenin interact as a potential new component of the Wnt signaling pathway

Pathologic gene network rewiring implicates PPP1R3A as a central regulator in pressure overload heart failure

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and perturbed respiratory metabolism. Mice lacking PPP1R3A are protected against pressure-overload heart failure. We present a global gene interaction map of the human heart failure transition, identify previously unreported cardiac eQTLs, and demonstrate the discovery potential of disease-specific networks through the description of PPP1R3A as a central regulator in heart failure

Bistability in Apoptosis by Receptor Clustering

Apoptosis is a highly regulated cell death mechanism involved in many physiological processes. A key component of extrinsically activated apoptosis is the death receptor Fas, which, on binding to its cognate ligand FasL, oligomerize to form the death-inducing signaling complex. Motivated by recent experimental data, we propose a mathematical model of death ligand-receptor dynamics where FasL acts as a clustering agent for Fas, which form locally stable signaling platforms through proximity-induced receptor interactions. Significantly, the model exhibits hysteresis, providing an upstream mechanism for bistability and robustness. At low receptor concentrations, the bistability is contingent on the trimerism of FasL. Moreover, irreversible bistability, representing a committed cell death decision, emerges at high concentrations, which may be achieved through receptor pre-association or localization onto membrane lipid rafts. Thus, our model provides a novel theory for these observed biological phenomena within the unified context of bistability. Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our model also suggests a mechanism by which cells may function as bistable life/death switches independently of any such dynamics in their downstream components. Our results highlight the role of death receptors in deciding cell fate and add to the signal processing capabilities attributed to receptor clustering.Comment: Accepted by PLoS Comput Bio