Online Classification in 3D Urban Datasets Based on Hierarchical Detection

One of the most significant problems in the area of 3D range image processing is that of segmentation and classifi-cation from 3D laser range data, especially in real-time. In this work we introduce a novel multi-layer approach to the classification of 3D laser scan data. In particular, we build a hierarchical framework of online detection and identifica-tion procedures drawn from sequential analysis namely the CUSUM (Cumulative Sum) and SPRT (Sequential Proba-bility Ratio Test), both of which are low complexity algo-rithms. Each layer of algorithms builds upon the decisions made at the previous stage thus providing a robust frame-work of online decision making. In our new framework we are not only able to classify in coarse classes such as verti-cal, horizontal and/or vegetation but to also identify objects characterized by more subtle or gradual changes such as curbs or steps. Moreover, our new multi-layer approach combines information across scanlines and results in more accurate decision making. We perform experiments in com-plex urban scenes and provide quantitative results. 1

A Multilab Replication of the Ego Depletion Effect

There is an active debate regarding whether the ego depletion effect is real. A recent preregistered experiment with the Stroop task as the depleting task and the antisaccade task as the outcome task found a medium-level effect size. In the current research, we conducted a preregistered multilab replication of that experiment. Data from 12 labs across the globe (N = 1,775) revealed a small and significant ego depletion effect, d = 0.10. After excluding participants who might have responded randomly during the outcome task, the effect size increased to d = 0.16. By adding an informative, unbiased data point to the literature, our findings contribute to clarifying the existence, size, and generality of ego depletion

Direct Inhibition of GSK3β by the Phosphorylated Cytoplasmic Domain of LRP6 in Wnt/β-Catenin Signaling

Wnt/β-catenin signaling plays a central role in development and is also involved in a diverse array of diseases. Binding of Wnts to the coreceptors Frizzled and LRP6/5 leads to phosphorylation of PPPSPxS motifs in the LRP6/5 intracellular region and the inhibition of GSK3β bound to the scaffold protein Axin. However, it remains unknown how GSK3β is specifically inhibited upon Wnt stimulation. Here, we show that overexpression of the intracellular region of LRP6 containing a Ser/Thr rich cluster and a PPPSPxS motif impairs the activity of GSK3β in cells. Synthetic peptides containing the PPPSPxS motif strongly inhibit GSK3β in vitro only when they are phosphorylated. Microinjection of these peptides into Xenopus embryos confirms that the phosphorylated PPPSPxS motif potentiates Wnt-induced second body axis formation. In addition, we show that the Ser/Thr rich cluster of LRP6 plays an important role in LRP6 binding to GSK3β. These observations demonstrate that phosphorylated LRP6/5 both recruits and directly inhibits GSK3β using two distinct portions of its cytoplasmic sequence, and suggest a novel mechanism of activation in this signaling pathway

Hierarchical Modeling of Activation Mechanisms in the ABL and EGFR Kinase Domains: Thermodynamic and Mechanistic Catalysts of Kinase Activation by Cancer Mutations

Structural and functional studies of the ABL and EGFR kinase domains have recently suggested a common mechanism of activation by cancer-causing mutations. However, dynamics and mechanistic aspects of kinase activation by cancer mutations that stimulate conformational transitions and thermodynamic stabilization of the constitutively active kinase form remain elusive. We present a large-scale computational investigation of activation mechanisms in the ABL and EGFR kinase domains by a panel of clinically important cancer mutants ABL-T315I, ABL-L387M, EGFR-T790M, and EGFR-L858R. We have also simulated the activating effect of the gatekeeper mutation on conformational dynamics and allosteric interactions in functional states of the ABL-SH2-SH3 regulatory complexes. A comprehensive analysis was conducted using a hierarchy of computational approaches that included homology modeling, molecular dynamics simulations, protein stability analysis, targeted molecular dynamics, and molecular docking. Collectively, the results of this study have revealed thermodynamic and mechanistic catalysts of kinase activation by major cancer-causing mutations in the ABL and EGFR kinase domains. By using multiple crystallographic states of ABL and EGFR, computer simulations have allowed one to map dynamics of conformational fluctuations and transitions in the normal (wild-type) and oncogenic kinase forms. A proposed multi-stage mechanistic model of activation involves a series of cooperative transitions between different conformational states, including assembly of the hydrophobic spine, the formation of the Src-like intermediate structure, and a cooperative breakage and formation of characteristic salt bridges, which signify transition to the active kinase form. We suggest that molecular mechanisms of activation by cancer mutations could mimic the activation process of the normal kinase, yet exploiting conserved structural catalysts to accelerate a conformational transition and the enhanced stabilization of the active kinase form. The results of this study reconcile current experimental data with insights from theoretical approaches, pointing to general mechanistic aspects of activating transitions in protein kinases

Approved and experimental small-molecule oncology kinase inhibitor drugs: a mid-2016 overview

Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small-molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs have received regulatory approval for the treatment of a variety of cancers and the volume of reports on the discovery and development of kinase inhibitors has increased to an extent where it is now difficult—even for those working in the field—easily to keep an overview of the compounds that are being developed, as currently there are 231 such compounds, targeting 38 different protein and lipid kinases (not counting isoforms), in clinical use or under clinical investigation. The purpose of this review is thus to provide an overview of the biomedical rationales for the kinases being targeted on the one hand, and the design principles, as well as chemical, pharmacological, pharmaceutical, and toxicological kinase inhibitor properties, on the other hand. Two issues that are especially important in kinase inhibitor research, target selectivity and drug resistance, as well as the underlying structural concepts, are discussed in general terms and in the context of relevant kinases and their inhibitors

Making the Invisible Visible

The Bronze Age settlement of Papadiokampos is located in the coastal plain west of the Trachilos peninsula near Siteia in eastern Crete. It was discovered by Chrysa Sofianou of the 24th Ephorate of Prehistoric and Classical Antiquities of the Greek Ministry of Culture and is the focus of her ongoing research program. Assistance in mapping the Late Minoan harbor town has been provided by the Publication Team of the Institute for Aegean Prehistory Study Center for East Crete. Topographical mapp..

Abstract The Rufus System: Information Organization for Semi-Structured Data

While database systems provide good function for writing applications on structured data, computer system users are inundated wit.11 a flood of semi-structured information, such as documents, elec-tronic mail, programs, and images. Today, this in-formation is typically stored in filesystems that pro-vide limited support for organizing, searching, and operating upon this data. Current database systems are inappropriate for semi-structured information because they require that the data be translated to their data model, breaking all current applications that use the data. Although research in database systems has concentrated on extending them to han-dle more varieties of fully structured data, database systems provide important function that could help users of semi-structured informat,ion. The Rufus syst*em attacks the problems of semi-structured data. It provides searching, orga-nizing, and browsing for the semi-structured infor-mation commonly stored in computer systems. Ru-fus models information with an extensible object-oriented class hierarchy a.nd provides automatic clas-sification of user data within that hierarchy. Query access is provided to help users search for needed information. Various ways of structuring user infor-mation are provided to help users browse. Methods Permission to copy without fee all or part of this m.aterial is granted provided Ihat the copies are not m,ade or distributed for direct com.nrrrcial advantage, the VLDB copyrighf n.otice and the title of the pub-lication and its date appear! and n.otice is given tha