Calibration of the modified Bartlett-Lewis model using global optimization techniques and alternative objective functions

The calibration of stochastic point process rainfall models, such as of the Bartlett-Lewis type, suffers from the presence of multiple local minima which local search algorithms usually fail to avoid. To meet this shortcoming, four relatively new global optimization methods are presented and tested for their ability to calibrate the Modified Bartlett-Lewis Model. The list of tested methods consists of: the Downhill Simplex Method, Simplex-Simulated Annealing, Particle Swarm Optimization and Shuffled Complex Evolution. The parameters of these algorithms are first optimized to ensure optimal performance, after which they are used for calibration of the Modified Bartlett-Lewis model. Furthermore, this paper addresses the choice of weights in the objective function. Three alternative weighing methods are compared to determine whether or not simulation results (obtained after calibration with the best optimization method) are influenced by the choice of weights

Event-based Asynchronous Sparse Convolutional Networks

Event cameras are bio-inspired sensors that respond to per-pixel brightness changes in the form of asynchronous and sparse "events". Recently, pattern recognition algorithms, such as learning-based methods, have made significant progress with event cameras by converting events into synchronous dense, image-like representations and applying traditional machine learning methods developed for standard cameras. However, these approaches discard the spatial and temporal sparsity inherent in event data at the cost of higher computational complexity and latency. In this work, we present a general framework for converting models trained on synchronous image-like event representations into asynchronous models with identical output, thus directly leveraging the intrinsic asynchronous and sparse nature of the event data. We show both theoretically and experimentally that this drastically reduces the computational complexity and latency of high-capacity, synchronous neural networks without sacrificing accuracy. In addition, our framework has several desirable characteristics: (i) it exploits spatio-temporal sparsity of events explicitly, (ii) it is agnostic to the event representation, network architecture, and task, and (iii) it does not require any train-time change, since it is compatible with the standard neural networks' training process. We thoroughly validate the proposed framework on two computer vision tasks: object detection and object recognition. In these tasks, we reduce the computational complexity up to 20 times with respect to high-latency neural networks. At the same time, we outperform state-of-the-art asynchronous approaches up to 24% in prediction accuracy

Asynchronous Tracking-by-Detection on Adaptive Time Surfaces for Event-based Object Tracking

Event cameras, which are asynchronous bio-inspired vision sensors, have shown great potential in a variety of situations, such as fast motion and low illumination scenes. However, most of the event-based object tracking methods are designed for scenarios with untextured objects and uncluttered backgrounds. There are few event-based object tracking methods that support bounding box-based object tracking. The main idea behind this work is to propose an asynchronous Event-based Tracking-by-Detection (ETD) method for generic bounding box-based object tracking. To achieve this goal, we present an Adaptive Time-Surface with Linear Time Decay (ATSLTD) event-to-frame conversion algorithm, which asynchronously and effectively warps the spatio-temporal information of asynchronous retinal events to a sequence of ATSLTD frames with clear object contours. We feed the sequence of ATSLTD frames to the proposed ETD method to perform accurate and efficient object tracking, which leverages the high temporal resolution property of event cameras. We compare the proposed ETD method with seven popular object tracking methods, that are based on conventional cameras or event cameras, and two variants of ETD. The experimental results show the superiority of the proposed ETD method in handling various challenging environments.Comment: 9 pages, 5 figure

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer

Dendrimers are structurally well-defined, synthetic polymers with sizes and physicochemical properties often resembling those of biomacromolecules (e.g. proteins). As a result they are promising candidates for peptide-based vaccine delivery platforms. Herein, we established a synthetic pathway to conjugate a human papillomavirus (HPV) E7 protein-derived peptide antigen to a star-polymer to create a macromolecular vaccine candidate to treat HPV-related cancers. These conjugates were able to reduce tumor growth and eradicate E7-expressing TC-1 tumors in mice after a single immunization, without the help of any external adjuvant

A Bayesian view of murine seminal cytokine networks

It has long been established that active agents in seminal fluid are key to initiating and coordinating mating-induced immunomodulation. This is in part governed by the actions of a network of cytokine interactions which, to date, remain largely undefined, and whose interspecific evolutionary conservation is unknown. This study applied Bayesian methods to illustrate the interrelationships between seminal profiles of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 (p70), IL-13, IL-17, eotaxin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-gamma, keratinocyte-derived chemokine (KC), monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1) alpha, MIP-1beta, regulated on activation normal T cell expressed and secreted (RANTES), tumour necrosis factor (TNF)-alpha, leptin, inducible protein (IP)-10 and vascular endothelial growth factor (VEGF) in a rat model. IL-2, IL-9, IL-12 (p70), IL-13, IL-18, eotaxin, IFN-gamma, IP-10, KC, leptin, MCP-1, MIP-1alpha and TNF-alpha were significantly higher in serum, whilst IL-1beta, IL-5, IL-6, IL-10, IL-17, G-CSF and GM-CSF were significantly higher in seminal fluid. When compared to mouse profiles, only G-CSF was present at significantly higher levels in the seminal fluid in both species. Bayesian modelling highlighted key shared features across mouse and rat networks, namely TNF-alpha as the terminal node in both serum and seminal plasma, and MCP-1 as a central coordinator of seminal cytokine networks through the intermediary of KC and RANTES. These findings reveal a marked interspecific conservation of seminal cytokine networks

The Transcriptome of Trichuris suis – First Molecular Insights into a Parasite with Curative Properties for Key Immune Diseases of Humans

Iatrogenic infection of humans with Trichuris suis (a parasitic nematode of swine) is being evaluated or promoted as a biological, curative treatment of immune diseases, such as inflammatory bowel disease (IBD) and ulcerative colitis, in humans. Although it is understood that short-term T. suis infection in people with such diseases usually induces a modified Th2-immune response, nothing is known about the molecules in the parasite that induce this response.As a first step toward filling the gaps in our knowledge of the molecular biology of T. suis, we characterised the transcriptome of the adult stage of this nematode employing next-generation sequencing and bioinformatic techniques. A total of ∼65,000,000 reads were generated and assembled into ∼20,000 contiguous sequences ( = contigs); ∼17,000 peptides were predicted and classified based on homology searches, protein motifs and gene ontology and biological pathway mapping.These analyses provided interesting insights into a number of molecular groups, particularly predicted excreted/secreted molecules (n = 1,288), likely to be involved in the parasite-host interactions, and also various molecules (n = 120) linked to chemokine, T-cell receptor and TGF-β signalling as well as leukocyte transendothelial migration and natural killer cell-mediated cytotoxicity, which are likely to be immuno-regulatory or -modulatory in the infected host. This information provides a conceptual framework within which to test the immunobiological basis for the curative effect of T. suis infection in humans against some immune diseases. Importantly, the T. suis transcriptome characterised herein provides a curated resource for detailed studies of the immuno-molecular biology of this parasite, and will underpin future genomic and proteomic explorations

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004