Timelines Are Expressive Enough to Capture Action-Based Temporal Planning

Planning problems are usually expressed by specifying which actions can be performed to obtain a given goal. In temporal planning problems, actions come with a time duration and can overlap in time, which noticeably increase the complexity of the reasoning process. Action-based temporal planning has been thoroughly studied from the complexity-theoretic point of view, and has been proved to be EXPSPACE-complete in its general formulation. Conversely, timeline-based planning problems are represented as a collection of variables whose time-varying behavior is governed by a set of temporal constraints, called synchronization rules. Timelines provide a unified framework to reason about planning and execution under uncertainty. Timeline-based systems are being successfully employed in real-world complex tasks, but, in contrast to action-based planning, little is known on their computational complexity and expressiveness. In particular, a comparison of the expressiveness of the action- and timeline-based formalisms is still missing. This paper contributes a first step in this direction by proving the EXPSPACE-completeness of timeline-based planning with no temporal horizon and bounded temporal relations only. The result is shown via a reduction from action-based temporal planning, thus proving that timelines are expressive enough to capture it

A Game-Theoretic Approach to Timeline-Based Planning with Uncertainty

In timeline-based planning, domains are described as sets of independent, but interacting, components, whose behaviour over time (the set of timelines) is governed by a set of temporal constraints. A distinguishing feature of timeline-based planning systems is the ability to integrate planning with execution by synthesising control strategies for flexible plans. However, flexible plans can only represent temporal uncertainty, while more complex forms of nondeterminism are needed to deal with a wider range of realistic problems. In this paper, we propose a novel game-theoretic approach to timeline-based planning problems, generalising the state of the art while uniformly handling temporal uncertainty and nondeterminism. We define a general concept of timeline-based game and we show that the notion of winning strategy for these games is strictly more general than that of control strategy for dynamically controllable flexible plans. Moreover, we show that the problem of establishing the existence of such winning strategies is decidable using a doubly exponential amount of space

The International Bathymetric Chart of the Arctic Ocean (IBCAO) Version 3.0

[1] The International Bathymetric Chart of the Arctic Ocean (IBCAO) released its first gridded bathymetric compilation in 1999. The IBCAO bathymetric portrayals have since supported a wide range of Arctic science activities, for example, by providing constraint for ocean circulation models and the means to define and formulate hypotheses about the geologic origin of Arctic undersea features. IBCAO Version 3.0 represents the largest improvement since 1999 taking advantage of new data sets collected by the circum-Arctic nations, opportunistic data collected from fishing vessels, data acquired from US Navy submarines and from research ships of various nations. Built using an improved gridding algorithm, this new grid is on a 500 meter spacing, revealing much greater details of the Arctic seafloor than IBCAO Version 1.0 (2.5 km) and Version 2.0 (2.0 km). The area covered by multibeam surveys has increased from ∼6% in Version 2.0 to ∼11% in Version 3.0

Automated multi-subject fiber clustering of mouse brain using dominant sets

Mapping of structural and functional connectivity may provide deeper understanding of brain function and disfunction. Diffusion Magnetic Resonance Imaging (DMRI) is a powerful technique to non-invasively delineate white matter (WM) tracts and to obtain a three-dimensional description of the structural architecture of the brain. However, DMRI tractography methods produce highly multi-dimensional datasets whose interpretation requires advanced analytical tools. Indeed, manual identification of specific neuroanatomical tracts based on prior anatomical knowledge is time-consuming and prone to operator-induced bias. Here we propose an automatic multi-subject fiber clustering method that enables retrieval of group-wise WM fiber bundles. In order to account for variance across subjects, we developed a multi-subject approach based on a method known as Dominant Sets algorithm, via an intra- and cross-subject clustering. The intra-subject step allows us to reduce the complexity of the raw tractography data, thus obtaining homogeneous neuroanatomically-plausible bundles in each diffusion space. The cross-subject step, characterized by a proper space-invariant metric in the original diffusion space, enables the identification of the same WM bundles across multiple subjects without any prior neuroanatomical knowledge. Quantitative analysis was conducted comparing our algorithm with spectral clustering and affinity propagation methods on synthetic dataset. We also performed qualitative analysis on mouse brain tractography retrieving significant WM structures. The approach serves the final goal of detecting WM bundles at a population level, thus paving the way to the study of the WM organization across groups.Mapping of structural and functional connectivity may provide deeper understanding of brain function and disfunction. Diffusion Magnetic Resonance Imaging (DMRI) is a powerful technique to non-invasively delineate white matter (WM) tracts and to obtain a three-dimensional description of the structural architecture of the brain. However, DMRI tractography methods produce highly multi-dimensional datasets whose interpretation requires advanced analytical tools. Indeed, manual identification of specific neuroanatomical tracts based on prior anatomical knowledge is time-consuming and prone to operator-induced bias. Here we propose an automatic multi-subject fiber clustering method that enables retrieval of group-wise WM fiber bundles. In order to account for variance across subjects, we developed a multi-subject approach based on a method known as Dominant Sets algorithm, via an intra-and cross-subject clustering. The intra-subject step allows us to reduce the complexity of the raw tractography data, thus obtaining homogeneous neuroanatomically-plausible bundles in each diffusion space. The cross-subject step, characterized by a proper space-invariant metric in the original diffusion space, enables the identification of the same WM bundles across multiple subjects without any prior neuroanatomical knowledge. Quantitative analysis was conducted comparing our algorithm with spectral clustering and affinity propagation methods on synthetic dataset. We also performed qualitative analysis on mouse brain tractography retrieving significant WM structures. The approach serves the final goal of detecting WM bundles at a population level, thus paving the way to the study of the WM organization across groups

Updated standardized definitions for efficacy endpoints in adjuvant breast cancer clinical trials: STEEP Version 2.0

Purpose The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007, provide standardized definitions of adjuvant breast cancer clinical trial end points. Given the evolution of breast cancer clinical trials and improvements in outcomes, a panel of experts reviewed the STEEP criteria to determine whether modifications are needed.Methods We conducted systematic searches of ClinicalTrials.gov for adjuvant systemic and local-regional therapy trials for breast cancer to investigate if the primary end points reported met STEEP criteria. On the basis of common STEEP deviations, we performed a series of simulations to evaluate the effect of excluding non-breast cancer deaths and new nonbreast primary cancers from the invasive disease-free survival end point.Results Among 11 phase III breast cancer trials with primary efficacy end points, three had primary end points that followed STEEP criteria, four used STEEP definitions but not the corresponding end point names, and four used end points that were not included in the original STEEP manuscript. Simulation modeling demonstrated that inclusion of second nonbreast primary cancer can increase the probability of incorrect inferences, can decrease power to detect clinically relevant efficacy effects, and may mask differences in recurrence rates, especially when recurrence rates are low.Conclusion We recommend an additional end point, invasive breast cancer-free survival, which includes all invasive disease-free survival events except second nonbreast primary cancers. This end point should be considered for trials in which the toxicities of agents are well-known and where the risk of second primary cancer is small. Additionally, we provide end point recommendations for local therapy trials, low-risk populations, noninferiority trials, and trials incorporating patient-reported outcomes

Screening and Initial Binding Assessment of Fumonisin B1 Aptamers

Fumonisins are mycotoxins produced by Fusarium verticillioides and F. proliferatum, fungi that are ubiquitous in corn (maize). Insect damage and some other environmental conditions result in the accumulation of fumonisins in corn-based products worldwide. Current methods of fumonisin detection rely on the use of immunoaffinity columns and high-performance liquid chromatography (HPLC). The use of aptamers offers a good alternative to the use of antibodies in fumonisin cleanup and detection due to lower costs and improved stability. Aptamers are single-stranded oligonucleotides that are selected using Systematic Evolution of Ligands by EXponential enrichment (SELEX) for their ability to bind to targets with high affinity and specificity. Sequences obtained after 18 rounds of SELEX were screened for their ability to bind to fumonisin B1. Six unique sequences were obtained, each showing improved binding to fumonisin B1 compared to controls. Sequence FB1 39 binds to fumonisin with a dissociation constant of 100 ± 30 nM and shows potential for use in fumonisin biosensors and solid phase extraction columns

Body circumferences: clinical implications emerging from a new geometric model

<p>Abstract</p> <p>Background</p> <p>Body volume expands with the positive energy balance associated with the development of adult human obesity and this "growth" is captured by two widely used clinical metrics, waist circumference and body mass index (BMI). Empirical correlations between circumferences, BMI, and related body compartments are frequently reported but fail to provide an important common conceptual foundation that can be related to key clinical observations. A two-phase program was designed to fill this important gap: a geometric model linking body volume with circumferences and BMI was developed and validated in cross-sectional cohorts; and the model was applied to the evaluation of longitudinally monitored subjects during periods of voluntary weight loss. Concepts emerging from the developed model were then used to examine the relations between the evaluated clinical measures and body composition.</p> <p>Methods</p> <p>Two groups of healthy adults (n = 494 and 1499) were included in the cross-sectional model development/testing phase and subjects in two previous weight loss studies were included in the longitudinal model evaluation phase. Five circumferences (arm, waist, hip, thigh, and calf; average of sum, C), height (H), BMI, body volume (V; underwater weighing), and the volumes of major body compartments (whole-body magnetic resonance imaging) were measured.</p> <p>Results</p> <p>The evaluation of a humanoid geometric model based a cylinder confirmed that V derived from C and H was highly correlated with measured V [R²both males and females, 0.97; p < 0.001). Developed allometric models confirmed model predictions that C and BMI (represented as V/H) are directly linked as, C = (V/H)^0.5. The scaling of individual circumferences to V/H varied, with waist the highest (V/H^~0.6) and calf the lowest (V/H^~0.3), indicating that the largest and smallest between-subject "growth" with greater body volume occurs in the abdominal area and lower extremities, respectively. A stepwise linear regression model including all five circumferences²showed that each contributed independently to V/H. These cross-sectional observations were generally confirmed by analysis of the two longitudinal weight loss studies. The scaling of circumference ratios (e.g., waist/hip) to V/H conformed to models developed on the scaling of individual circumferences to V/H, indicating their relations to BMI are predictable <it>a priori</it>. Waist, hip, and arm/calf circumferences had the highest associations with whole-body visceral adipose tissue, subcutaneous adipose tissue, and skeletal muscle volumes, respectively.</p> <p>Conclusion</p> <p>These observations provide a simple geometric model relating circumferences with body size and composition, introduce a conceptual foundation explaining previous empirical observations, and reveal new clinical insights.</p

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Engineering Multi-Agent Systems: State of Affairs and the Road Ahead

The continuous integration of software-intensive systems together with the ever-increasing computing power offer a breeding ground for intelligent agents and multi-agent systems (MAS) more than ever before. Over the past two decades, a wide variety of languages, models, techniques and methodologies have been proposed to engineer agents and MAS. Despite this substantial body of knowledge and expertise, the systematic engineering of large-scale and open MAS still poses many challenges. Researchers and engineers still face fundamental questions regarding theories, architectures, languages, processes, and platforms for designing, implementing, running, maintaining, and evolving MAS. This paper reports on the results of the 6th International Workshop on Engineering Multi-Agent Systems (EMAS 2018, 14th-15th of July, 2018, Stockholm, Sweden), where participants discussed the issues above focusing on the state of affairs and the road ahead for researchers and engineers in this area

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure