9,864 research outputs found

    Active Learning of Multiple Source Multiple Destination Topologies

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    We consider the problem of inferring the topology of a network with MM sources and NN receivers (hereafter referred to as an MM-by-NN network), by sending probes between the sources and receivers. Prior work has shown that this problem can be decomposed into two parts: first, infer smaller subnetwork components (i.e., 11-by-NN's or 22-by-22's) and then merge these components to identify the MM-by-NN topology. In this paper, we focus on the second part, which had previously received less attention in the literature. In particular, we assume that a 11-by-NN topology is given and that all 22-by-22 components can be queried and learned using end-to-end probes. The problem is which 22-by-22's to query and how to merge them with the given 11-by-NN, so as to exactly identify the 22-by-NN topology, and optimize a number of performance metrics, including the number of queries (which directly translates into measurement bandwidth), time complexity, and memory usage. We provide a lower bound, N2\lceil \frac{N}{2} \rceil, on the number of 22-by-22's required by any active learning algorithm and propose two greedy algorithms. The first algorithm follows the framework of multiple hypothesis testing, in particular Generalized Binary Search (GBS), since our problem is one of active learning, from 22-by-22 queries. The second algorithm is called the Receiver Elimination Algorithm (REA) and follows a bottom-up approach: at every step, it selects two receivers, queries the corresponding 22-by-22, and merges it with the given 11-by-NN; it requires exactly N1N-1 steps, which is much less than all (N2)\binom{N}{2} possible 22-by-22's. Simulation results over synthetic and realistic topologies demonstrate that both algorithms correctly identify the 22-by-NN topology and are near-optimal, but REA is more efficient in practice

    Ancient and historical systems

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    A roadmap to integrate astrocytes into Systems Neuroscience.

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    Systems neuroscience is still mainly a neuronal field, despite the plethora of evidence supporting the fact that astrocytes modulate local neural circuits, networks, and complex behaviors. In this article, we sought to identify which types of studies are necessary to establish whether astrocytes, beyond their well-documented homeostatic and metabolic functions, perform computations implementing mathematical algorithms that sub-serve coding and higher-brain functions. First, we reviewed Systems-like studies that include astrocytes in order to identify computational operations that these cells may perform, using Ca2+ transients as their encoding language. The analysis suggests that astrocytes may carry out canonical computations in a time scale of subseconds to seconds in sensory processing, neuromodulation, brain state, memory formation, fear, and complex homeostatic reflexes. Next, we propose a list of actions to gain insight into the outstanding question of which variables are encoded by such computations. The application of statistical analyses based on machine learning, such as dimensionality reduction and decoding in the context of complex behaviors, combined with connectomics of astrocyte-neuronal circuits, is, in our view, fundamental undertakings. We also discuss technical and analytical approaches to study neuronal and astrocytic populations simultaneously, and the inclusion of astrocytes in advanced modeling of neural circuits, as well as in theories currently under exploration such as predictive coding and energy-efficient coding. Clarifying the relationship between astrocytic Ca2+ and brain coding may represent a leap forward toward novel approaches in the study of astrocytes in health and disease

    Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease.

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    BackgroundThere are no effective treatments or validated clinical response markers in systemic sclerosis (SSc). We assessed imaging biomarkers and performed gene expression profiling in a single-arm open-label clinical trial of tyrosine kinase inhibitor dasatinib in patients with SSc-associated interstitial lung disease (SSc-ILD).MethodsPrimary objectives were safety and pharmacokinetics. Secondary outcomes included clinical assessments, quantitative high-resolution computed tomography (HRCT) of the chest, serum biomarker assays and skin biopsy-based gene expression subset assignments. Clinical response was defined as decrease of >5 or >20% from baseline in the modified Rodnan Skin Score (MRSS). Pulmonary function was assessed at baseline and day 169.ResultsDasatinib was well-tolerated in 31 patients receiving drug for a median of nine months. No significant changes in clinical assessments or serum biomarkers were seen at six months. By quantitative HRCT, 65% of patients showed no progression of lung fibrosis, and 39% showed no progression of total ILD. Among 12 subjects with available baseline and post-treatment skin biopsies, three were improvers and nine were non-improvers. Improvers mapped to the fibroproliferative or normal-like subsets, while seven out of nine non-improvers were in the inflammatory subset (p = 0.0455). Improvers showed stability in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), while both measures showed a decline in non-improvers (p = 0.1289 and p = 0.0195, respectively). Inflammatory gene expression subset was associated with higher baseline HRCT score (p = 0.0556). Non-improvers showed significant increase in lung fibrosis (p = 0.0313).ConclusionsIn patients with SSc-ILD dasatinib treatment was associated with acceptable safety profile but no significant clinical efficacy. Patients in the inflammatory gene expression subset showed increase in skin fibrosis, decreasing pulmonary function and worsening lung fibrosis during the study. These findings suggest that target tissue-specific gene expression analyses can help match patients and therapeutic interventions in heterogeneous diseases such as SSc, and quantitative HRCT is useful for assessing clinical outcomes.Trial registrationClinicaltrials.gov NCT00764309

    Network-provider-independent overlays for resilience and quality of service.

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    PhDOverlay networks are viewed as one of the solutions addressing the inefficiency and slow evolution of the Internet and have been the subject of significant research. Most existing overlays providing resilience and/or Quality of Service (QoS) need cooperation among different network providers, but an inter-trust issue arises and cannot be easily solved. In this thesis, we mainly focus on network-provider-independent overlays and investigate their performance in providing two different types of service. Specifically, this thesis addresses the following problems: Provider-independent overlay architecture: A provider-independent overlay framework named Resilient Overlay for Mission-Critical Applications (ROMCA) is proposed. We elaborate its structure including component composition and functions and also provide several operational examples. Overlay topology construction for providing resilience service: We investigate the topology design problem of provider-independent overlays aiming to provide resilience service. To be more specific, based on the ROMCA framework, we formulate this problem mathematically and prove its NP-hardness. Three heuristics are proposed and extensive simulations are carried out to verify their effectiveness. Application mapping with resilience and QoS guarantees: Assuming application mapping is the targeted service for ROMCA, we formulate this problem as an Integer Linear Program (ILP). Moreover, a simple but effective heuristic is proposed to address this issue in a time-efficient manner. Simulations with both synthetic and real networks prove the superiority of both solutions over existing ones. Substrate topology information availability and the impact of its accuracy on overlay performance: Based on our survey that summarizes the methodologies available for inferring the selective substrate topology formed among a group of nodes through active probing, we find that such information is usually inaccurate and additional mechanisms are needed to secure a better inferred topology. Therefore, we examine the impact of inferred substrate topology accuracy on overlay performance given only inferred substrate topology information

    Making microscopy count: quantitative light microscopy of dynamic processes in living plants

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    First published: April 2016This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Cell theory has officially reached 350 years of age as the first use of the word ‘cell’ in a biological context can be traced to a description of plant material by Robert Hooke in his historic publication “Micrographia: or some physiological definitions of minute bodies”. The 2015 Royal Microscopical Society Botanical Microscopy meeting was a celebration of the streams of investigation initiated by Hooke to understand at the sub-cellular scale how plant cell function and form arises. Much of the work presented, and Honorary Fellowships awarded, reflected the advanced application of bioimaging informatics to extract quantitative data from micrographs that reveal dynamic molecular processes driving cell growth and physiology. The field has progressed from collecting many pixels in multiple modes to associating these measurements with objects or features that are meaningful biologically. The additional complexity involves object identification that draws on a different type of expertise from computer science and statistics that is often impenetrable to biologists. There are many useful tools and approaches being developed, but we now need more inter-disciplinary exchange to use them effectively. In this review we show how this quiet revolution has provided tools available to any personal computer user. We also discuss the oft-neglected issue of quantifying algorithm robustness and the exciting possibilities offered through the integration of physiological information generated by biosensors with object detection and tracking

    Optogenetic Brain Interfaces

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    The brain is a large network of interconnected neurons where each cell functions as a nonlinear processing element. Unraveling the mysteries of information processing in the complex networks of the brain requires versatile neurostimulation and imaging techniques. Optogenetics is a new stimulation method which allows the activity of neurons to be modulated by light. For this purpose, the cell-types of interest are genetically targeted to produce light-sensitive proteins. Once these proteins are expressed, neural activity can be controlled by exposing the cells to light of appropriate wavelengths. Optogenetics provides a unique combination of features, including multimodal control over neural function and genetic targeting of specific cell-types. Together, these versatile features combine to a powerful experimental approach, suitable for the study of the circuitry of psychiatric and neurological disorders. The advent of optogenetics was followed by extensive research aimed to produce new lines of light-sensitive proteins and to develop new technologies: for example, to control the distribution of light inside the brain tissue or to combine optogenetics with other modalities including electrophysiology, electrocorticography, nonlinear microscopy, and functional magnetic resonance imaging. In this paper, the authors review some of the recent advances in the field of optogenetics and related technologies and provide their vision for the future of the field.United States. Defense Advanced Research Projects Agency (Space and Naval Warfare Systems Center, Pacific Grant/Contract No. N66001-12-C-4025)University of Wisconsin--Madison (Research growth initiative; grant 101X254)University of Wisconsin--Madison (Research growth initiative; grant 101X172)University of Wisconsin--Madison (Research growth initiative; grant 101X213)National Science Foundation (U.S.) (MRSEC DMR-0819762)National Science Foundation (U.S.) (NSF CAREER CBET-1253890)National Institutes of Health (U.S.) (NIH/NIBIB R00 Award (4R00EB008738)National Institutes of Health (U.S.) (NIH Director’s New Innovator award (1-DP2-OD002989))Okawa Foundation (Research Grant Award)National Institutes of Health (U.S.) (NIH Director’s New Innovator Award (1DP2OD007265))National Science Foundation (U.S.) (NSF CAREER Award (1056008)Alfred P. Sloan Foundation (Fellowship)Human Frontier Science Program (Strasbourg, France) (Grant No. 1351/12)Israeli Centers of Research Excellence (I-CORE grant, program 51/11)MINERVA Foundation (Germany
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