Open-Retrieval Conversational Question Answering

Conversational search is one of the ultimate goals of information retrieval. Recent research approaches conversational search by simplified settings of response ranking and conversational question answering, where an answer is either selected from a given candidate set or extracted from a given passage. These simplifications neglect the fundamental role of retrieval in conversational search. To address this limitation, we introduce an open-retrieval conversational question answering (ORConvQA) setting, where we learn to retrieve evidence from a large collection before extracting answers, as a further step towards building functional conversational search systems. We create a dataset, OR-QuAC, to facilitate research on ORConvQA. We build an end-to-end system for ORConvQA, featuring a retriever, a reranker, and a reader that are all based on Transformers. Our extensive experiments on OR-QuAC demonstrate that a learnable retriever is crucial for ORConvQA. We further show that our system can make a substantial improvement when we enable history modeling in all system components. Moreover, we show that the reranker component contributes to the model performance by providing a regularization effect. Finally, further in-depth analyses are performed to provide new insights into ORConvQA.Comment: Accepted to SIGIR'2

Human Immunodeficiency Virus type 1 Endocytic Trafficking Through Macrophage Bridging Conduits Facilitates Spread of Infection

Bridging conduits (BC) sustain communication and homeostasis between distant tethered cells. These are also exploited commonly for direct cell-to-cell transfer of microbial agents. Conduits efficiently spread infection, effectively, at speeds faster than fluid phase exchange while shielding the microbe against otherwise effective humoral immunity. Our laboratory has sought to uncover the mechanism(s) for these events for human immunodeficiency virus type one (HIV-1) infection. Indeed, in our prior works HIV-1 Env and Gag antigen and fluorescent virus tracking were shown sequestered into endoplasmic reticulum-Golgi organelles but the outcomes for spreading viral infection remained poorly defined. Herein, we show that HIV-1 specifically traffics through endocytic compartments contained within BC and directing such macrophage-to-macrophage viral transfers. Following clathrin-dependent viral entry, HIV-1 constituents bypass degradation by differential sorting from early to Rab11+ recycling endosomes and multivesicular bodies. Virus-containing endocytic viral cargoes propelled by myosin II through BC spread to neighboring uninfected cells. Disruption of endosomal motility with cytochalasin D, nocodasole and blebbistatin diminish intercellular viral spread. These data lead us to propose that HIV-1 hijacks macrophage endocytic and cytoskeletal machineries for high-speed cell-to-cell spread

Actin Dynamics Regulate Multiple Endosomal Steps during Kaposi's Sarcoma-Associated Herpesvirus Entry and Trafficking in Endothelial Cells

The role of actin dynamics in clathrin-mediated endocytosis in mammalian cells is unclear. In this study, we define the role of actin cytoskeleton in Kaposi's sarcoma-associated herpesvirus (KSHV) entry and trafficking in endothelial cells using an immunofluorescence-based assay to visualize viral capsids and the associated cellular components. In contrast to infectivity or reporter assays, this method does not rely on the expression of any viral and reporter genes, but instead directly tracks the accumulation of individual viral particles at the nuclear membrane as an indicator of successful viral entry and trafficking in cells. Inhibitors of endosomal acidification reduced both the percentage of nuclei with viral particles and the total number of viral particles docking at the perinuclear region, indicating endocytosis, rather than plasma membrane fusion, as the primary route for KSHV entry into endothelial cells. Accordingly, a viral envelope protein was only detected on internalized KSHV particles at the early but not late stage of infection. Inhibitors of clathrin- but not caveolae/lipid raft-mediated endocytosis blocked KSHV entry, indicating that clathrin-mediated endocytosis is the major route of KSHV entry into endothelial cells. KSHV particles were colocalized not only with markers of early and recycling endosomes, and lysosomes, but also with actin filaments at the early time points of infection. Consistent with these observations, transferrin, which enters cells by clathrin-mediated endocytosis, was found to be associated with actin filaments together with early and recycling endosomes, and to a lesser degree, with late endosomes and lysosomes. KSHV infection induced dynamic actin cytoskeleton rearrangements. Disruption of the actin cytoskeleton and inhibition of regulators of actin nucleation such as Rho GTPases and Arp2/3 complex profoundly blocked KSHV entry and trafficking. Together, these results indicate an important role for actin dynamics in the internalization and endosomal sorting/trafficking of KSHV and clathrin-mediated endocytosis in endothelial cells

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease:an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN)

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 μm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician’s considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal

The Politics of Bicycle Innovation: Comparing the American and Dutch Human-Powered Vehicle Movements, 1970s—present

This paper deals with the history of the international Human-Powered Vehicle (HPV) movement, originally launched in the 1970s by engineers and scientists who believed that bicycle innovation could give a major impetus to a coveted western bicycle renaissance. Based on a reading of magazines and books from the American and Dutch HPV scenes, it compares ideas and practices within the Dutch Human-Powered Vehicle association NVHPV (established 1984) with those of the American-based IHPVA (established 1976), asking why the American ideas about innovative Human-Powered Vehicles did not evoke a stronger response in a bicycle-friendly country such as the Netherlands. The paper shows that while new ideas to promote cycling may travel easily, national trajectories and cultures of cycling prove remarkably resilient to change. KEYWORDS: bicycle renaissance; environmentalism; glocalization; Human-Powered Vehicle movement; IHPVA; innovation; Netherland

Erkundung und Sanierung eines Mineraloelschadensfalles unter Flugvorfeldbedingungen Standortsituation und Sanierungskonzeption

Unter dem Flugvorfeld der Rhein-Main Air Base wurde im Juni 1989 ein massiver alter Kerosinschaden entdeckt. Neben der auf dem Grundwasser aufschwimmenden Kerosinphase wurde im Grundwasser eine erhebliche Belastung mit geloesten Kohlenwasserstoffen, insbesondere Benzol und Toluol, nachgewiesen. Der Schadensfall liegt in der Trinkwasserschutzzone III der Wasserwerke Hinkelstein. Der Vortrag beschreibt die erforderlichen Erkundungen und Untersuchungen und stellt das Sanierungskonzept vor, dessen Ziel es war, die Ausbreitung der Kerosinlinse auf dem Grundwasser zu verhindern, die Kerosinphase abzuschoepfen und das kontaminierte Grundwasser sowie den Boden langfristig zu regenerieren. Bei der Sanierungsplanung wurden wirtschaftliche und technische Loesungen entwickelt, die unter den schwierigen Randbedingungen des laufenden militaerischen Flughafenbetriebes und einer geplanten Neubaumassnahme im Schadensbereich ausfuehrbar sind. (orig./GG)In June 1989, a massive old kerosene damage was discovered under the apron of Rhein-Main Air Base. In addition to the kerosene phase floating on top of the ground water, a considerable contamination with solute hydrocarbons, in particular benzene and toluene, was detected. The damage site is located within the Drinking Water Protection Zone III of the Hinkelstein Waterworks. This presentation describes the required soundings and investigations and presents the rehabilitation concept which was designed to prevent the kerosene lens from expanding and to regenerate both the contaminated ground water and soil in the long-run. Rehabilitation planning involved the development of economic and engineering solutions which can be implemented under the difficult marginal conditions of current military airfield operations and the planned construction of a new building within the damage area. (orig./GG)SIGLEAvailable from TIB Hannover: D.Dt.F. AC 1000(39,23) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman